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Multidisciplinary
Approach to
Osteoporosis
From Assessment
to Treatment
Andrea Lenzi
Silvia Migliaccio
Editors
123
Multidisciplinary Approach to Osteoporosis
Andrea Lenzi • Silvia Migliaccio
Editors
Multidisciplinary
Approach to Osteoporosis
From Assessment to Treatment
Editors
Andrea Lenzi Silvia Migliaccio
Department of Experimental Medicine Department of Movement, Human and
Sapienza University of Rome Health Sciences
Rome Foro Italico University of Rome
Italy Rome
Italy
ISBN 978-3-319-75108-5 ISBN 978-3-319-75110-8 (eBook)

https://doi.org/10.1007/978-3-319-75110-8
Library of Congress Control Number: 2018949650
© Springer International Publishing AG, part of Springer Nature 2018

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Preface
I ntroduction to Interdisciplinary Approach to Osteoporosis:

Why Is It So Important?
Osteoporosis is a skeletal metabolic disorder that has reached epidemic extents all
over the industrialized world. Recent epidemiological studies confirm the tendency
to a dramatic increase of individuals affected by osteoporosis and fragility fractures.
Indeed, during the last decades, for the increase of life expectancy, this disease has
become a major health threat around the world. Age, both in male and female popu-
lation, increases the risk of developing osteoporosis, which affects millions of
women, but lately, also men. Age-related changes in body composition, metabolic
factors, and hormonal levels, accompanied by a decline in physical activity, may all
provide mechanisms for the propensity to lose muscle mass, gain fat mass, and also
develop bone loss.
Since many factors, such as genetic, environmental, nutritional, and hormonal,
play an important role in determining this disorder, attention must be given to this
health problem by researchers, politicians, the media, and the public in order to
approach this skeletal alteration in a correct manner. In fact, osteoporosis is one of
the most common chronic disorders in the industrialized societies, with an impor-
tant impact on individual lives as well as on health economics (medical expenses,
lost income as a result of disability, and complications of fragility fractures), and
therefore, this skeletal disorder has become a major factor in health care planning
systems due to the high socioeconomic costs.
Most reports agree that, among other factors, lack of physical activity and non-
equilibrated nutrition play a role in the development of bone loss, altered skeletal
homeostasis, and, thus, skeletal fragility.
The genetic basis of osteoporosis has been studied analyzing the role of different
gene products, and an increase in knowledge suggests the role of different cyto-
kines, hormones, and their receptors, indicating that genetic factors might play an
important role in osteoporosis development besides all other known factors.
Thus, it appears clear that osteoporosis, being a multifactorial chronic skeletal
disease, needs an interdisciplinary approach in order to accomplish all the needs of
patients affected by osteoporosis and fragility fractures.
v
vi Preface
Indeed, many programs and advice are starting to be offered to the public. Many
educational programs centered on nutritional intervention, physical activity, and
pharmacological therapy are considered vital to improve the knowledge of this dis-
ease in order to reduce fragility fractures and to diminish disability and mortality
and to improve quality of life of individuals affected by osteoporosis.
In this book, the authors’ contributions address the spectrum of the multidisci-
plinary, and interdisciplinary, approach to osteoporosis, ranging from physiological
characteristics to epidemiology, to clinical characteristics and pharmacological
approaches. Metabolic and endocrinological aspects of obesity are analyzed in
depth, considering the role of thyroid, adrenal, and ovarian functions, the interaction
between osteoporosis and obesity or sarcopenia or kidney or rheumatological dis-
eases. Clinical aspects are considered, starting from the multidisciplinary evaluation
(clinical, nutritional, functional) through the different interventions (therapeutic
education and physical activity and training prescription, prescription medications),
up to the interdisciplinary management of osteoporosis.
The involvement of experts in nutrition, kidney diseases, endocrinology and
andrology, rheumatology, exercise and sports medicine, and orthopedic surgery
explains, the multidisciplinary approach that should characterize the clinical care of
the patient affected by osteoporosis.
The experts of the different disciplines, who have been involved in this editorial
project, have made every effort to produce manuscripts rich in evidence-based med-
icine contents, but also basic research, highlighting the importance of a translational
approach “from the bench to the bedside” pointing viewpoints from multiple disci-
plines and the multilayered issues involved in the care of patients affected by
osteoporosis.
The book will be useful to physicians, scientists, postgraduate students, and stu-
dents of various disciplines dealing with osteoporosis and fragility fractures.
Rome, Italy Andrea Lenzi

Rome, Italy Silvia Migliaccio
Contents
1 Anatomy and Physiology of Skeletal Tissue: The Bone Cells�� 1

Giacomina Brunetti, Graziana Colaianni, Silvia Colucci,
and Maria Grano
2 Genetics of Osteoporosis�� 25
Francesca Marini, Laura Masi, Gemma Marcucci, Luisella
Cianferotti, and Maria Luisa Brandi
3 Osteoporosis Diagnosis�� 45
Claudio Marcocci and Federica Saponaro
4 Functional Evaluation of the Subjects with Skeletal Alterations�� 59
Giovanni Iolascon, Alessandro de Sire, Marco Paoletta, Antimo
Moretti, and Francesca Gimigliano
Part I Endocrinologicic and Metabolic Regulation

5 Skeletal Alterations and Parathyroid Function�� 75
Elisabetta Romagnoli and Vincenzo Carnevale
6 GH/IGF-I and Bone �� 83
Stefano Frara, Filippo Maffezzoni, Mauro Doga, Anna Maria
Formenti, Gherardo Mazziotti, and Andrea Giustina
7 Adrenal Function and Skeletal Regulation�� 107
Iacopo Chiodini, Claudia Battista, Elisa Cairoli, Cristina Eller-
Vainicher, Valentina Morelli, Serena Palmieri, Antonio Stefano
Salcuni, and Alfredo Scillitani
8 Skeletal Tissue and Ovarian Function: Puberty and Menopause �� 129
Annamaria Colao, Carolina Di Somma, and Volha V. Zhukouskaya
9 Obesity and Osteoporosis: Is the Paradigm Changing?�� 143
Emanuela A. Greco, Rachele Fornari, Andrea Lenzi,
and Silvia Migliaccio
vii
viii Contents
10 Bone and Diabetes�� 153

Andrea Palermo, Anda Mihaela Naciu, Gaia Tabacco, Luca
D’Onofrio, and Nicola Napoli
11 Renal Diseases and Skeletal Health�� 183
Sandro Mazzaferro, Silverio Rotondi, Lida Tartaglione, Natalia De
Martino, Cristiana Leonangeli, and Marzia Pasquali
12 Osteoporosis and Cardiovascular Risk�� 211
Giancarlo Isaia, Lorenzo Marchese, Margherita Marchetti,
and Mario Bo
13 Osteoporosis in Men�� 223
Elena Nebot Valenzuela and Peter Pietschmann
14 Rheumatic Diseases and Osteoporosis �� 237
Ombretta Di Munno, Nazzarena Malavolta, and Giovanni Minisola
Part II Prevention and Treatment

15 Nutrition and Skeletal Health �� 259
Chiara Marocco, Rachele Fornari, Andrea Lenzi,
and Emanuela A. Greco
16 Different Physical Activity Protocols in the Subjects Affected by
Osteoporosis�� 277
Gian Pietro Emerenziani, Emanuela A. Greco, Laura Guidetti,
and Carlo Baldari
17 Pharmacological Therapy: Past, Present, and Future�� 285
Silvia Migliaccio, Andrea Lenzi, and Emanuela A. Greco
18 Surgical Therapy: Vertebro-Cifoplastic: – Pros and Cons�� 297
Umberto Tarantino, Giuseppina Resmini, Alessando Provenza,
Eleonora Piccirilli, Maurizio Feola, and Riccardo Iundusi
19 Rehabilitation Therapy After Surgery in Osteoporotic Patients�� 313
Francesca Gimigliano, Alessandro de Sire, Antimo Moretti, Claudio
Curci, and Giovanni Iolascon
Index�� 325
Anatomy and Physiology of Skeletal
Tissue: The Bone Cells 1
Giacomina Brunetti, Graziana Colaianni, Silvia Colucci,
and Maria Grano
1.1 Introduction
The skeleton is a hard structure formed by a set of bones that support the human
body. According to their shape, the bones can be classified into four groups: long
bones, short bones, flat bones, and irregular bones. Long bones, the major bones of
limbs, are longer than they are wide and consist of an elongated central hollow
shaft, known as diaphysis, and two expanded ends, known as epiphysis. The part
between the diaphysis and the epiphysis is called metaphysis. The inner portion of
the bone includes a cavity, known as marrow or medullary cavity, filled with bone
marrow. Short bones are almost equivalent in length and diameter (i.e., the carpal
bones of the hand); flat bones are skinny and plate-like (i.e., the skull and the ster-
num); irregular bones have a different shape with respect to the previously described
three groups of bones (i.e., a vertebra).
Bone exists in two main forms due to the arrangement of collagen fibers: woven
bone and lamellar bone. Woven bone is an immature form characterized by a disor-
ganized disposition of collagen fibers, thereby resulting in a weaker structure.
Lamellar bone is the mature form and displays a regular parallel alignment of col-
lagen fibrils arranged in lamellae.
The mature bone tissue is structurally divided into two types: the cortical/com-
pact bone and the spongy trabecular bone. Cortical bone is dense and solid and
surrounds the marrow cavity, whereas trabecular bone is composed of a network of
trabecular plates and rods strewed in the bone marrow compartment. Mature
G. Brunetti · S. Colucci
Department of Basic and Medical Sciences, Neurosciences and Sense Organs,
Section of Human Anatomy and Histology, University of Bari, Bari, Italy
G. Colaianni · M. Grano (*)
Department of Emergency and Organ Transplantation, Section of Human
Anatomy and Histology, University of Bari, Bari, Italy
e-mail: maria.grano@uniba.it
© Springer International Publishing AG, part of Springer Nature 2018 1

A. Lenzi, S. Migliaccio (eds.), Multidisciplinary Approach to Osteoporosis,
https://doi.org/10.1007/978-3-319-75110-8_1
2 G. Brunetti et al.
cortical bone is mainly composed of cylindrical units known as osteons or Haversian

systems, which are formed by concentric lamellae of bone matrix containing a cen-
tral neurovascular canal.
As all the other connective tissue, the bone consists of an extracellular matrix
composed of an inorganic and organic part and a cellular component, consisting of
osteoclasts (OCs), osteoblasts (OBs), and osteocytes. The major component of the
inorganic matrix is hydroxyapatite, whereas the organic part includes primarily col-
lagen type 1 but also other non-collagenic proteins, such as osteopontin, osteocal-
cin, and proteoglycans.
1.2 The Functions of the Bone
The bone is currently considered a multifunctional tissue. Indeed, it plays roles in

mechanical support, provides a structure for the attachment of muscles, and allows
body movements. The bone also exerts a protection for different organs, especially
in vital areas such as the trunk, in which the ribcage shields the lungs and the heart
or the vertebrae protect the spinal cord, or also cranial bones which kept the brain
safe. Furthermore, the bone stores several minerals, such as calcium and phospho-
rus, which, when required, are released from the bone in the blood taking part in
mineral homeostasis. In addition, the bone plays a role in hematopoiesis since all
cellular blood components are derived from hematopoietic stem cells present in the
bone marrow, the soft tissue hosted inside the cavity of the long bones and trabecu-
lar spaces, and also acts as energy storage due to yellow marrow, which, containing
lipids, represents an energy reservoir. More recently, it has become clear that the
bone can also display an endocrine function, as it regulates not only itself but also
other organs through the two most well-known and well-studied molecules: osteo-
calcin (OCN) and fibroblast growth factor 23 (FGF23) [1].
Exclusively, the bone renews itself throughout the life through the physiological
process known as bone remodeling consisting in the balanced activity of OCs, the
resorptive cells of the bone, and OBs, the bone-building cells. Recently, more and
more evidences have indicated that the osteocytes, the most abundant bone cell type
embedded in the mineralized matrix, orchestrate bone remodeling.
Here we will address the current knowledge about bone cells.
1.3 Osteoclasts
OCs, generated by fusion of myeloid precursors [2], are multinucleated cells pres-
ent in physiological condition on bone surfaces when extracellular matrix degrada-
tion occurs. OCs have an exclusive cytoskeletal organization and membrane
polarization that allows them to isolate the bone-apposed extracellular space, “the
Howship’s lacunae,” where bone resorption takes place. Through their resorption
activity OCs absolve to numerous functions. First of all, they participate to renew
1 Anatomy and Physiology of Skeletal Tissue: The Bone Cells 3
the bone in order to maintain its homeostasis. Secondly, since the bone is the major
organ for the calcium storage, OCs are sensitive to numerous signal regulating cal-
cium release from the bone, such as parathyroid hormone and 1,25(OH)2 vitamin
D3. Thirdly, through bone-resorbing activity, OCs are responsible of the release of
growth factors stored in the bone matrix including insulin-like growth factor-1
(IGF-1) and transforming growth factor β (TGF-β) affecting the coupling of bone
formation and resorption and targeting other cells in the bone microenvironment.
Lastly, OCs maintain characteristics of other myeloid cells, such as cytokine release
and antigen presentation, which give them the potential to influence immune
responses.
Bone Resorption
OCs adhere to bone matrix by integrin αvβ3, expressed in specialized F-actin
structures called podosomes; surround the portion of the bone to be digested
and polarized in way that the cellular membrane in front of the bone is convo-
luted by the presence of microvilli, “the “ruffled border”; and hold the proton
pump (V-ATPase) and Cl− channel 7 (ClC7), whereas the basolateral mem-
brane domain includes the HCO3−/Cl− antiporter [2]. Cytoplasmic carbonic
anhydrase type II (CAII) enzyme creates the protons to be released into the
resorption Howship’s lacuna under the cell. This “space” becomes separated
from the rest of the extracellular space through the tight binding of αvβ3 to the
bone matrix at the sealing zone. The β3 cytoplasmic domain recruits signaling
proteins, inducing the binding of actin with different molecules (including
vinculin, kindlin, talin, paxillin, and myosin IIA) and formation of the actin
ring that labels the periphery of the ruffled membrane. Combined activity of
ClC7 and V-ATPase determines elevated levels of HCl that acidifies the
Howship’s lacuna, leading to the solubilization of the inorganic compounds of
the bone matrix. In parallel, acidified cytoplasmic vesicles containing lyso-
somal enzymes including cathepsin K and metalloprotease-9 are also trans-
ported toward the ruffled cell membrane and, ultimately, released in the
lacunae to degrade the organic components of the bone matrix.
1.4 Osteoclastogenesis
The primary factors regulating OC differentiation are MCSF and RANKL, pro-
duced by stromal and OB lineage cells thereby providing support for this process [3,
4]. Beyond macrophage colony-stimulating factor (MCSF) and receptor activator of
nuclear factor-κB ligand (RANKL), the normal bone marrow microenvironment
also contains a wide variety of OC-regulating molecules, including cytokines,
growth factors, and hormones which are discussed in detail below.
MCSF
MCSF is derived from osteoblastic cells and is involved in the growth and
survival of the OCs through regulation of numerous pathways such as the
mitogen-activated protein kinases (MAPKs), extracellular signal-regulated
kinase (ERK), and Jun N-terminal kinase (JNK) [4], glycogen synthase
kinase-3β/β-catenin [5], and mammalian target of rapamycin (mTOR) [6].
Moreover, MCSF also induces OC differentiation signals since it has been
recently found to increase diacylglycerol levels through stimulation of phos-
pholipase C-γ (PLC-γ), which in turn causes c-Fos activation [7]. The MCSF
actions are mediated by binding with its receptor c-fms, and the importance of
the growth factor and its receptor in osteoclastogenesis and bone phenotype
came from data showing that null mutations in either the ligand or the recep-
tor genes result in a severe osteopetrosis [8]. Recently, it has been demon-
strated that c-fms can also interact with the newly identified interleukin-34
(IL-34) and that MCSF as well as IL-34 promote the expression of RANK,
whose signaling pathways also promote osteoclastogenesis [9].
RANKL/RANK/OPG Axis
RANKL is another crucial factor required for the differentiation, survival, and
function of OCs. Two decades ago the demonstrations that RANKL transgenic
mice showed osteoporosis whereas mice knockout for RANKL or for the decoy
receptor osteoprotegerin (OPG) are osteopetrotic [10] and osteoporotic [11],
respectively, underline the crucial function of this pathway in osteoclastogenesis.
Furthermore, human osteoclast-poor osteopetrosis has been associated to inacti-

vation or deficiency of RANKL [12]. Inactivation of OPG causes juvenile Paget’s
disease [13], a high-turnover bone disorder, whereas activating mutations of RANK
generates different osteolytic diseases, such as familial expansile osteolysis [14].
Monocytes expressing RANK, a tumor necrosis factor (TNF) receptor family
member, in the presence of RANKL fuse to differentiate into multinucleated OCs.
RANKL–RANK interaction leads to the activation of numerous pathways including
MAPKs (p38, JNK, ERK), mTOR, PI3K, NF-κB (canonical and alternative), and
microphthalmia-associated transcription factor (MITF) [6, 15, 16].
Some of these pathways induce the expression of nuclear factor of activated T
cells, cytoplasmic 1 (NFATc1), the key osteoclastogenic transcription factor [17],
whose activation is also linked to the PLC-γ2/Ca2+ pathway. RANK signaling deter-
mines protein posttranslational modifications such as ubiquitination [18] (72), phos-
phorylation [19], and SUMOylation [20]. Ongoing studies also demonstrate a
crucial role of epigenetic mechanisms in RANKL control of osteoclastogenesis [21,
22]. In fact, RANKL modulates the expression of several microRNAs [23]. RANKL
also determines histone 3 (H3) lysine 4 trimethylation (H3K4me3, a mark of
transcriptionally active chromatin) whereas mitigates H3K27me3 (a mark of silent

chromatin) near the transcription start site of several genes encoding OC transcrip-
tion factors, such as NFATc1 and NF-κB [24].
Recently, Luo et al. reported that leucine-rich repeat-containing G-protein-
coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL. LGR4
competes with RANK to bind RANKL and inhibited canonical RANK signaling
during osteoclastogenesis [25]. RANKL binding to LGR4 activates the Gaq and
GSK3-β signaling pathway, thereby inhibiting the expression and activity of
NFATC1 during OC differentiation. Both total (Lgr4−/−) and monocyte conditional
knockout mice of Lgr4 (Lgr4 CKO) showed increased OC formation and activity.
The same authors demonstrated that LGR4 extracellular domain therapeutically
abrogated RANKL-induced bone loss in three mouse models of osteoporosis [25].
OSCAR, FcRγ, and DAP12

A third signal controlling osteoclastogenesis arises from ITAM adaptors includ-
ing DNAX activation protein of 12 kDa (DAP12) [26] and Fc receptor γ (FcRγ).
These cell surface molecules interact with co-receptors TREM2 and Sirpβ1
(DAP12) or OSCAR and PIR-A (FcRγ) in order to activate Ca2+/NFATc1
through PLC-γ2 [27, 28]. In mice, deletion of either ITAM protein has no effect
on bone mass, while deletion of both causes severe osteopetrosis. Other studies
reported that the primary role of the ITAM-mediated signaling seems to be in the
regulation of the OC cytoskeleton, with modest effect on osteoclastogenesis [26,
29]. Furthermore, loss of TREM2, the co-receptor for DAP12, increases OC for-
mation, through β-catenin, indicative of a Ca2+/NFATc1-independent effect [2].
Thus, ITAM signaling role in osteoclastogenesis requires further studies.
Tumor Necrosis Factor-α (TNF-α)

Already before the discovery of RANKL pro-osteoclastogenic role, TNF-α was
recognized for its ability to stimulate bone resorption in vivo and in vitro [30,
31]. TNF-α stimulates RANKL and MCSF expression by osteoblastic cells and
also binds directly OC precursors [32, 33]. Numerous signaling pathways acti-
vated by TNF-α and RANKL are very similar and together stimulate OC dif-
ferentiation [34, 35]. However, the ability of TNF-α alone to induce
osteoclastogenesis is quite low, due to little diversities in signaling pathway. In
detail, RANK engages TRAF3, allowing the processing of p100 to p52, thereby
removing significant brakes on the alternative NF-κB signaling pathway [36].
TNFR1 signaling augments p100 levels but not its transformation to p52.
Another molecule that negatively affect TNF-α pro- osteoclastogenic effect is

RBP-J, a transcription factor which if it is removed leads to strong osteolysis in
response to TNF-α [37]. In normal cells, small amounts of RANKL with TNF-α have
a synergic on osteoclastogenesis. However, in conditions in which RANKL is severely

excluded from the system, exposure of precursors to TNF-α prior to RANKL inhibits
osteoclastogenesis [34]. Due to the presence of a death domain in TNFR1, TNFα
stimulates pro-apoptotic pathways in addition to the pro-survival pathways that are
downstream of classical NF-κB. Thus, the addition of TNF-α to OCs or their precur-
sors causes apoptosis only when classical NF-κB is blocked. Thus, NF-κB signaling
downstream of TNFα supplies a strong survival signal to OC lineage cells.
LIGHT
LIGHT (homologous to Lymphotoxins exhibiting Inducible expression and
competing with herpes simplex virus Glycoprotein D for herpes virus entry
mediator [HVEM], a receptor expressed by T lymphocytes) is a member of
TNFSF (TNFSF14) expressed on activated T cells, natural killer cells, mono-
cytes, granulocytes, spleen cells, and immature dendritic cells [38–40]. LIGHT
can engage two membrane-bound TNFSF signaling receptors, HVEM and lym-
photoxin beta receptor (LTβR). HVEM is expressed on endothelial, dendritic,
natural killer, and T and B cells [41, 42], while LTβR is expressed on fibroblast,
monocyte, endothelial, epithelial, and stromal cells [43]. Following the interac-
tion of LIGHT with HVEM or LTβR resulted in cytokine production and cell
survival or proliferation [44–47]. The LIGHT–LTβR interaction can also lead to
cell death [48, 49]. Through the interaction with HVEM, LIGHT is described as
a potent T cell co-stimulatory molecule [41, 50, 51]; its constitutive expression
on T cells causes activation and expansion of these cells, favoring autoimmune
disease development [52, 53]. LIGHT could also bind a soluble receptor decoy
receptor 3 (DcR3), which is known to be involved in OC formation [54].
Moreover, LIGHT has been implicated in osteolytic rheumatoid arthritis and
multiple myeloma [55, 56], although conflicting results have been reported about
the role of LIGHT on OC formation [55–59]. In particular, Hishida et al. reported
no OC differentiation from peripheral blood (PB) CD14+ monocytes treated with
LIGHT [55], whereas our previous work in agreement with what demonstrated
by Edwards et al. and Hemingway et al. showed a LIGHT pro-osteoclastogenic
effect [56–59]. However, all the cited authors concordantly reported that LIGHT
and RANKL synergically stimulated OC formation [55–59].
Interleukin-17 (IL-17)
Interleukins are known to affect OC differentiation [60, 61]. Recently, IL-17
attracted numerous scientists overall for the therapeutic implications. IL-17 is
expressed by a type of human T-helper cell (Th17) [61]. This cytokine plays a
crucial role in inflammation and the development of autoimmune diseases
such as rheumatoid arthritis; however, its mechanism of action in the develop-
ment of bone erosions, especially in relation to other known key cytokines
such as IL-1, TNF, and RANKL, remains unclear.
IL-17 has been demonstrated to be implicated in osteoclastogenesis augmenta-

tion in inflammation by increasing the release of RANKL, which may synergize
with IL-1 and TNF [62].
1.5 Osteoblasts
OBs differentiate from mesenchymal stem cells (MSCs), sharing their origin with
other cells of connective tissues such as fibroblasts, adipocytes, and chondrocytes.
They represent only 5% of total bone resident cells that are mainly constituted by
osteocytes. OBs have the crucial function of building the bone [63] but also of
regulating OC differentiation through the production of MCSF, RANKL, and
OPG [3, 64].
Osteoblastogenesis is defined by several steps: lineage commitment, prolifera-
tive expansion, synthesis and mineralization of bone matrix, and differentiation in
osteocytes. All these stages are signed by specific activation of transcription factors
and sequential gene transcription thereby determining the expression of the typical
OB markers. The key transcription factors involved in osteoclastogenesis are
RUNX2 and Osterix, whereas the typical OB markers include collagen I (COLL I),
alkaline phosphatase (ALP), bone sialoprotein, osteonectin, osteopontin, and OCN.
1.6 Transcription Factors Affecting Osteoblastogenesis
Runt domain-containing transcription factor (Runx2) represents a master switch for

osteoblastogenesis. Runx2 levels progressively enhance during osteoblastogenesis,
reaching the maximum expression in complete differentiated OBs. Runx2 homozy-
gous deletion in mice determined a total lack of OBs [65], whereas Runx2 haploin-
sufficiency in mice or in humans led to hypoplastic clavicles and delayed closure of
the fontanelles, defects that are typical of cleidocranial dysplasia in humans [66–
68]. RUNX2 is necessary for the suitable activity of mature OBs, including the
synthesis of bone matrix [69]. In fact Runx2 target genes include both genes
expressed by immature and differentiated OBs, such as TGF-β receptor, ALP, COLL
I, OPN, OCN, and collagenase [70].
Osterix (OSX)
OSX, transcription factor, is required downstream of RUNX2 and thereby
necessary for OB differentiation. In mouse embryos OSX deletion led to OB
absence, although RUNX2 is expressed [71]. These findings, together with
the demonstration that OSX levels were undetectable in RUNX2-null mice
[71], suggested that OSX works downstream of RUNX2 during osteoblasto-
genesis. OSX is essential both during embryogenesis and for postnatal OB
and osteocyte differentiation and activity [72].
Activating Transcription Factor 4 (ATF4)

ATF4, a member of the basic Leu zipper (bZIP) family of transcription fac-
tors, has a key role in mature OB lineage cells. Alteration of ATF4 activity has
been associated with the skeletal abnormalities observed in Coffin–Lowry
syndrome patients [73, 74]. ATF4 directly regulates the expression of the
bone matrix protein OCN and of RANKL. ATF4 also is involved in the amino
acid import to guarantee a suitable protein synthesis by OBs [73].
Activating Protein 1 (AP1)

AP1 is a transcription factor which consists of different dimers of proteins
belonging to Fos (c-Fos, FosB, Fra-1, and Fra-2) and Jun families (c-Jun,
JunB, and JunD) [75]. Conditional deletion of Fra-1 in mice resulted in osteo-
penia that seems to be due to the reduced expression of OCN and COLL I
[76]. Transgenic overexpression of FRA1 determined high bone mass due to
increased osteoblastogenesis [73–80]. Moreover, a direct transcriptional con-
trol of OCN and Coll I by Fra-2 in human subjects has been reported [77, 78].
Additionally, ΔFOSB transgenic mice, an isoform of FOSB, increased bone
mass through stimulation of OB formation and activity [79, 80].
1.7 Molecules Affecting Osteoblastogenesis
The WNT family of glycoproteins has crucial functions in the regulation of osteo-
blastogenesis. Following the binding to different transmembrane receptor, WNT
glycoproteins trigger several intracellular pathways that may be β-catenin depen-
dent or independent [81, 82].
In β-catenin-dependent WNT signaling, the glycoproteins (WNT1, WNT3,
WNT3A, WNT8, WNT9A, or WNT10B) engage frizzled receptors and their
co-receptors low-density lipoprotein receptor-related protein 5 (LRP5) or LRP6
leading to the activation of a cascade of intracellular mediators that stabilize
cytosolic β-catenin [83]. Thus, β-catenin translocates into the nucleus, interacts
with lymphoid enhancer-binding factor 1 (LEF1) and T cell factor 1 (TCF1),
TCF3, and TCF4 transcription factors, and promotes the transcription of osteo-
blastic genes. Wnt pathway is tightly regulated by numerous secreted antago-
nists that are soluble frizzled-related proteins (sFRPs), which interfere with Wnt/
frizzled receptor binding or Dickkopf (DKK) proteins and sclerostin, which bind
the co-receptor LRP5/6. Indeed, loss-of-function mutations in LRP5 gene cause
osteoporosis–pseudoglioma syndrome [84]. Mutations in LRP5 cause high bone
mass syndrome [85–89]. Whereas, mutations in SOST (which encodes scleros-
tin) result in sclerosteosis or Van Buchem disease, respectively [90–93]. Genetic
deletion of β-catenin in embryonic mesenchymal progenitors abolishes mature

OB generation [94–97].
Noncanonical Wnt glycoproteins such as WNT5A, WNT5B, WNT6, WNT7B,
WNT11, and WNT16 can trigger the planar cell polarity (PCP) pathway or the Wnt/
Ca2+ signaling. The PCP pathway affects cell orientation in tissues as well as cell mobil-
ity, shape, differentiation, and communication. WNT5A is fundamental for controlling
the PCP pathway through a DSH, Ras homolog gene family member (RhoB) and the
small GTPase Rab4, activating kinases such as the c-Jun N-terminal kinase (JNK) con-
trolling cytoskeletal rearrangements [98, 99]. The Wnt/Ca2+ pathway triggers the activa-
tion of phospholipase C with consequent release of calcium that sequentially stimulates
NFAT [100, 101]. Calcium signaling is engaged for cell fate and cell migration.
WNT5A was first classified as a noncanonical Wnt that activates β-catenin-
independent pathways. However, recent studies demonstrated that the downstream
signaling of WNT5A can affect canonical β-catenin-dependent signaling [102].
Indeed depending on the receptor availability, noncanonical Wnts such as WNT5A or
WNT16 can trigger or even antagonize alternative pathways [102, 103]. Thus, the
division between canonical and noncanonical signaling pathways is becoming pro-
gressively more imprecise.
BMP Signaling
BMPs, a TGFβ superfamily member, bind to receptor complexes composed
of heterotetramers of type I and type II Ser/Thr kinase receptors and activate
SMADs (SMAD1, SMAD5, or SMAD8). The phosphorylated SMADs form
a complex with SMAD4 and translocate into the nucleus to regulate gene
expression. Genetic studies have shown that BMP2 and BMP4 signaling is
required for differentiation to mature OBs. Furthermore, mice lacking only
BMP2 in the limb mesenchyme formed bone during embryogenesis but
exhibited a clear defect in bone mineral density shortly after birth, resulting in
frequent fractures that failed to heal [104]. Deletion of BMP receptor 1A
(BMPR1A) in pre-osteoblasts and OBs, either in utero or postnatally, resulted
in an unexpected increase in bone mass [105–107]. These studies indicated
that, although BMPR1A loss decreased bone formation, it also reduced bone
resorption to a greater extent, resulting in a net increase in bone mass. Thus,
BMP signaling in OB lineage cells seems to also have an important role in
regulating OCs. In addition to its role in OB differentiation, BMP signaling
regulates the function of mature OBs. Deletion of BMPR1A in mature OBs
decreased OB function [108], whereas overexpression of noggin, a secreted
inhibitor for BMPs, caused a reduction in OB function and a lower bone mass
in mice postnatally [109]. Similarly, deletion of SMAD4 in mature OBs
impaired OB activity [110]. Interestingly, BMP3 may counteract BMP2 and
BMP4 activity to maintain a proper bone mass in vivo, as BMP3 knockout
mice had increase trabecular bone respect to wild-type mice.
Semaphorins
Semaphorins emerged as a family of cell surface attached or secreted pro-
teins. The semaphorins are grouped into eight major classes [111]: the first
seven are ordered by number, from class 1 to class 7; the eighth group is class
V (V stands for virus). Classes 1 and 2 are found in invertebrates only, while
classes 3, 4, 6, and 7 are found in vertebrates only. Class 5 is found in both
vertebrates and invertebrates, and class V is specific to viruses. Most sema-
phorins use receptors in the group of proteins known as plexins. Class 3 sema-
phorins signal through heterocomplexes of neuropilins, class A plexins, and
cell adhesion molecules; class 7 semaphorin use integrins as their receptors.
Recently, it emerged the role of semaphorins in the regulation of bone cell
activity. In detail, Sema3A is abundantly expressed in bone, and cell-based
assays showed that Sema3A affected OB differentiation [112]. Semaphorin
3A (Sema3A) has an osteoprotective effect by both inhibiting bone resorption
and promoting bone formation. The binding of Sema3A to neuropilin-1
(Nrp1) suppressed RANKL-induced osteoclastogenesis. Furthermore,
Sema3A and Nrp1 binding promotes osteoblastogenesis and suppresses adi-
pogenesis through canonical Wnt/β-catenin pathway [112]. In mice Sema3A
injection augmented bone volume and accelerated bone regeneration. Further
studies showed that osteoblast-specific Sema3A-deficient mice had normal
bone mass [113]. In contrast, mice lacking Sema3A in neurons had low bone
mass, comparable to Sema3a-KO mice, signifying that neuron-derived
Sema3A is responsible for the observed bone alterations independent of the
local effect of Sema3A in the bone [113].
OCs express semaphorin 4D (Sema4D), which strongly suppresses bone forma-

tion [114]. On OBs the binding of Sema4D to its receptor plexin-B1 resulted in the
suppression of IGF-1 signaling and by modulating OB motility. Sema4d−/− mice
and Plxnb1−/− mice specifically in OBs showed increased bone mass due to aug-
mented bone formation. Notably, mice treatment with Sema4D neutralizing anti-
body prevented bone loss in postmenopausal osteoporosis murine model.
Semaphorin 7A (SEMA7A) has been shown to play a crucial role in the acti-
vation of monocyte/macrophages, thus contributing to osteoclastogenesis
[115]. Polymorphisms of the SEMA7A gene were associated with low bone
mineral density of the lumbar spine and femoral neck and with risk of vertebral
fracture [116].
Semaphorin 3B (SEMA3B) has been identified as a 1,25(OH)(2)D(3)-
stimulated gene in osteoblastic cells. Moreover, during OB differentiation
SEMA3B gene expression increased. Transgenic SEMA3B mice showed reduced
bone mineral density and altered trabecular bone, due to increased OC numbers
and activity [117].
Collectively, these studies support the key role of semaphorins in the regulation
of skeletal homeostasis.
Lipocalin-2
Lipocalin-2 (LCN2) is a 25-kD adipokine belonging to a large superfamily of
proteins that bind and transport lipids and other hydrophobic molecules. In
mice subjected to experimentally induced mechanical unloading, Lcn2
expression was upregulated in the long bones [118]. In primary OBs trans-
fected with LCN2-expression-vector (OBs-Lcn2), the levels of Runx2,
Osterix, and Alp were downregulated, whereas IL-6 mRNA and the Rankl/
Opg ratio were p-regulated. These findings suggest that LCN2 directly affect
osteoblastogenesis and indirectly osteoclastogenesis [118].
The Myokine Irisin

Irisin was originally identified as hormone-like myokine, secreted from skeletal
muscle in response to exercise both in mice and humans, and able to induce the
so-called browning response in white adipose tissue [119]. However, latest evi-
dence has questioned the primary biological role of irisin, demonstrating that
irisin also targets bone tissue directly, driving positive effects on cortical mineral
density and improving bone strength and geometry in mice [120]. This study
highlighted a new biological significance of irisin as one of the molecules
responsible for the yet poorly characterized bone-muscle unit and suggested that
irisin might be the link between physical exercise and healthy bone. The effect of
irisin on the bone is mainly exerted on OB lineage by enhancing differentiation
and activity of bone-forming cells, through the upregulation of the Atf4. The
increased differentiation and activity of OBs were also proved by the enhance-
ment of ALP-positive colonies and nodules of mineralized matrix. Consistently,
the expression of ALP and COLL I mRNA were upregulated by irisin treatment
in vitro [120, 121]. Although its receptor has not been identified yet, the action of
irisin on OB is receptor mediated, as demonstrated by the activation of the MAP
kinases Erk and p38 upon r-irisin administration in vitro [120–122].
In vivo data also showed higher Atf4 expression in bone marrow of irisin-treated
mice, suggesting a substantial commitment of OB precursor toward osteogenesis. In
addition, long bones of r-irisin-treated mice expressed high level of osteopontin,
one of the most abundant protein of bone matrix that is also known to be a mechani-
cally responsive molecule [123], and strongly reduced expression of sclerostin, one
of the inhibitors of the bone anabolic Wnt pathway [124].
1.8 Osteocytes
Osteocytes, the most abundant cells in the bone, are essential for the maintenance of
skeletal homeostasis. Osteocytes orchestrate bone formation during growth and the
preservation of a healthy skeletal frame for locomotion. These cells modulate OB
and OC activity by releasing factors that allow the skeleton to respond to mechani-
cal needs and hormonal variation. Osteocytes participate to bone endocrine func-
tions by producing hormones that influence other tissues/organs and control mineral
metabolism as well as hematopoiesis.
1.9 Osteocytogenesis
About 5–20% of OBs resident on the bone surface are progressively surrounded by
the bone matrix proteins they secrete and became osteocytes [125, 126]. This dif-
ferentiation process is delineated by changes in gene expression and is associated to
functional and morphological changes. The active OBs have cuboidal shape, large
nucleus located near the basal membrane of the cell, and copious endoplasmic retic-
ulum and Golgi apparatus. During osteocytogenesis, organelle number strongly
declines, and the nuclear-to-cytoplasm volume ratio enhances as cells attain a star-
like morphology. The cytoplasmic processes of osteocytes are localized in the cana-
liculi of the mineralized bone and interact with adjacent osteocytes, cells on the
bone surface, and endothelial cells of blood vessels. This wide lacunar–canalicular
system is preserved by osteocyte capability to remodel their neighboring space. The
osteocyte lacunar–canalicular system also permits the diffusion of osteocyte-pro-
duced molecules among all the cells of the bone and the bone marrow. Genes that
are modulated during osteocytogenesis can be divided, based on their function, into
three groups: genes associated to dendritic morphology and canaliculi formation,
genes linked to phosphate metabolism and matrix mineralization, and genes modu-
lating bone formation or resorption.
1.9.1 Development and Maintenance of the Osteocytic Network
The differentiation from OBs to osteocytes is mediated by several proteins control-

ling the development of dendrites and the mineralization and matrix degradation to
guarantee the proper formation of the lacunar–canaliculi system.
Podoplanin
Podoplanin is expressed in newly embedded osteocytes, but not in mature
osteocytes or in OBs on the bone surface, thereby podoplanin is a marker of
early osteocyte differentiation [127]. Podoplanin expression is necessary for
elongation of the dendrite and is augmented by mechanical stimulation both
in vitro and in vivo. Podoplanin interacts with CD44, and their expression has
been linked with dendrite branching of the osteocytes [128, 129]. Osteocytic
dendrites also have α-actinin and fimbrin, key proteins for cytoskeletal orga-
nization of osteocytes isolated from chicken [130, 131].
Dentin Matrix Acidic Phosphoprotein-1 (DMP-1)

DMP-1 is expressed in mature OBs, and its expression enhances as OBs dif-
ferentiate toward osteocytes [132]. DMP-1 is necessary for suitable osteocyte
maturation. Indeed, in mice lacking DMP1 osteocytes expressed elevated lev-
els of osteoblastic and early osteocytic genes (such as those podoplanin) and
low levels of sclerostin (a marker of mature osteocytes) [133]. Additionally,
these mice have defective mineralization and disorganized osteocytic lacu-
nar–canalicular system.
MMPs
The expression of MMPs also progressively increases as OBs differentiate
into osteocytes. In osteocytogenesis MMP role can be associated to their
function to cleave collagen in the matrix surrounding osteocytes, thereby
allowing the formation of canaliculi through which osteocytes extend cyto-
plasmic projections. Consistently, in mice MMP-14 deletion led to few or
absent osteocytic processes [134]. Moreover, MMP-13 is required to maintain
osteocyte viability [135].
Connexin 43 (CX43)
CX43, critical protein for the activity of the osteocyte network, forms gap
junction channels between communicating cells; CX43 also forms hemichan-
nels connecting cells with the extracellular environment. In mice CX43 dele-
tion from osteocytes reduces their viability and determines modifications in
long bone geometry [136–138]. In vitro CX43 knockdown leads to cells that
die spontaneously and express an increased RANKL/OPG ratio [138].
Furthermore, in CX43 knockout mice, OCs are localized on bone surfaces
neighboring to areas where apoptotic osteocytes accumulate, suggesting that
signals by dying osteocytes are crucial for OC recruitment.
1.9.2 Phosphate Metabolism and Matrix Mineralization
During osteocytogenesis the genes of the phosphate metabolism and matrix miner-
alization are highly expressed 35. These genes include fibroblast growth factor 23
(FGF23), DMP-1, matrix extracellular phosphoglycoprotein (MEPE), phosphate-
regulating neutral endopeptidase (PHEX), and fetuin-A. FGF23 is expressed by
osteocytes and affects phosphate metabolism by targeting the kidney. FGF23 inter-
acts with FGF receptors and klotho co-receptor in the renal proximal tubule, which
results into inhibition of renal phosphate reabsorption [139]. Fgf23 knockout mice
showed hyperphosphatemia, decreased BMD, reduced bone formation, and accu-

mulation of unmineralized osteoid [140].
FGF23 also works in an autocrine and/or paracrine way in osteocytes and other bone
cells, as FGF receptor 1 (FGFR1) and klotho are also present on these cells. Other osteo-
cyte-produced molecules affect FGF23 expression and/or function and consequently
indirectly influence phosphate metabolism. Indeed, in humans inactivating mutations in
DMP1 or PHEX lead to high levels of FGF23 and hypophosphatemia [141].
DMP-1 is necessary for correct bone mineralization, whereas MEPE is an inhibi-
tor of the mineralization whose deletion in mice leads to increased bone mineral
density [142]. DMP-1 and MEPE expression is increased by loading, and these
proteins might mediate the local outcomes of mechanical stimulation in the matrix
neighboring osteocytes [143]. Enzymatic degradation of MEPE generates a peptide
that blocks mineralization both in vitro and in vivo [144]. PHEX is a metalloendo-
peptidase that interacts with MEPE and its peptide. Phex knockout mice develops
osteomalacia and an altered osteocytic lacuna–canalicular system [145].
The liver protein fetuin-A, bone mineralization and calcification inhibitor, has
been found in the bone and is more expressed by osteocytes compared with OBs
[146]. Fetuin-A might be involved in the formation of dendrites by slowing matrix
calcification of the surroundings developing osteocytes. Thus, phosphate metabolism
regulation results from highly interconnected functions of these osteocytic proteins,
because changes in the levels of one of them modifies the expression of the others,
thereby generating a cascade of events that finally affects bone mineralization.
1.9.3 Regulation of Bone Formation and Resorption
Wnt Signaling
The Wnt antagonist DKK-1 is expressed in OBs and at higher levels in osteo-
cytes [147]. Another Wnt inhibitor, secreted frizzled-related protein-1 (SFRP-
1), is present in early osteocytes, and its expression decreases in mature
osteocytes [148]. Another Wnt signaling antagonist, sclerostin, is primarily
expressed in mature osteocytes and not in early osteocytes or OBs [149].
Sclerostin also binds to LRP4, which is required for the inhibitory action of
sclerostin on Wnt–βcatenin signaling [150]. Importantly, osteocyte-targeted
deletion of Lrp5 or overexpression of high bone mass LRP5 mutants in osteo-
cytes repeats the low or high bone mass phenotypes displayed by mice or
humans with the genetic modifications in all cells [151], suggesting that acti-
vation of the Wnt pathway in osteocytes is sufficient to achieve bone forma-
tion downstream of LRP5 [86, 151].
Osteocalcin (OCN), the most abundant non-collagenous protein present in the

bone, is an inhibitor of bone formation, as evidenced by the high bone mass in the
absence of defective bone mineralization or bone resorption in mice. OCN is a
marker of OBs. However, in mice OCN is expressed at higher levels in osteocytes

than in OBs [152], and osteocytes are more abundant than OBs. Osteocytes with the
OBs, therefore, possibly contribute to the pool of OCN in the circulation. Studies in
mice have also demonstrated that OCN in its undercarboxylated form can modulate
insulin secretion by pancreatic β-cells, insulin sensitivity and glucose uptake in
muscle, and fat metabolism [153].
RANKL
Osteocytes also secrete RANKL. In studies using genetically modified mice,
deletion of RANKL from osteocytes renders mice osteopetrotic, due to a
reduced number of OCs, decreased bone resorption, and a progressive increase
in bone mass [154], which suggests that osteocytes are an important source of
RANKL in the bone.
MCSF
Similar to MCSF knockout mice in all tissues, targeting deletion of MCSF in
osteocytes led to reduced OC numbers and osteopetrosis, demonstrating that
osteocytes are a key source of MCSF in the bone [155]. Osteocytes also
express c-fms, the receptors for MCSF [147], and mice lacking osteocytic
MCSF have osteocytes with abnormal morphology, a high prevalence of
apoptosis, and reduced gap junctions [155]. These results suggest that osteo-
cytes are both important source and target of MCSF.
OPG
The anti-osteoclastogenic molecule OPG is produced in both OBs and osteo-
cytes, and OPG mRNA levels are more profuse in osteocytes than in OBs
[156]. Moreover, OPG is a target of canonical Wnt signaling, and mice lack-
ing β-catenin in OBs and/or osteocytes show in the same way reduced OPG
levels, increased OC number, and low bone mass [156–158]. Therefore, the
modulation of osteocytic OPG by canonical Wnt signaling has key role in
bone resorption control.
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[12] Islington Wells, or the Threepenny Academy.
[13] Cp. E. Ward, “The Infallible Predictor” (Works, ii. p. 355,
ed. 1709).
[14] An advertisement of 23 May, 1712 (Percival’s Sadler’s
Wells announces the performances from six to ten in the morning
and from four till eight in the evening of two wonderful posture-
makers, a man and a child of nine, to take place in the dancing-
room of New Tunbridge Wells.
[15] Extract from family correspondence communicated by C.
L. S. to Notes and Queries, 8th ser. vi. 1894, p. 69.
[16] In 1760 the breakfasting was ninepence, the afternoon tea
sixpence, and the coffee eightpence. No stronger beverages were
sold.
[17] A serious attempt seems to have been made to keep this
rule. The London Daily Advertiser for 25 June, 1752, records that
a beautiful though notorious woman, who had appeared at the
dancing at New Tunbridge on June 24, was, on being recognised
by the company, turned out by a constable.
[18] Dr. Russel, who analysed the water about 1733, says that
it had a taste of iron and (unless mixed with common water) was
apt to make the drinker giddy or sleepy. This was the experience
of Lady Mary Wortley Montagu, who, however, expatiates on the
benefit she had derived from the Spa.
[19] This was between the main part of the Spa gardens and
St. John’s Street Road; cp. Wallis’s Plan, 1808.
[20] A band had played in the morning under Holland’s
management (advertisement in the Public Advertiser, 5 May,
1775).
[21] Malcolm, Lond. rediv. iii. 230, 231.
[22] The orchestra connected with it was pulled down in 1827;
Cromwell’s Clerkenwell, p. 357.
[23] No. 6, Eliza Place, stood on the site of the old entrance
(Pinks).
[24] Mr. Philip Norman, writing in Notes and Queries, 8th ser.
vi. 1894, p. 457, says:—“I have seen (in the cellar of No. 6, Spa
Cottages, behind the house at the corner of Lloyd’s Row) grotto
work with stone pilasters and on each side steps descending.
Here, I believe, was the chalybeate spring. For many years it has
ceased to flow.”
[25] Daily Telegraph, 1 August, 1895.
[26] A newspaper paragraph of April 1752, mentions the little
summer house at the Ducking Pond House in Spa Fields, as
being lately stripped of its chairs and tables by some pitiful
rogues.
[27] In The Macaroni and Theatrical Magazine for January
1773 (p. 162) is the notice:—
“Pantheons: The Nobility’s, Oxford Road; the Mobility’s,
Spawfields.”
[28] The organ appears, about 1772, to have been silenced on
Sundays, at least for a time. A correspondent in The Gazetteer
and New Daily Advertiser for 20 June, 1772, refers to the
Middlesex Justices who will not suffer the organs to be played at
the Little Pantheon, White Conduit House, Bagnigge Wells, &c.
[29] May Day, or the Origin of Garlands, a poem published in
1720. The Field Spy, published in 1714 (Rogers, Views of
Pleasure Gardens of London, p. 46), speaks of the spring and
garden as if a good deal frequented in 1714.
[30] A rare bronze ticket of oblong form, incised with the words,
“London Spaw No. 19,” is in the possession of Mr. W. T. Ready,
the London coin dealer. It may belong to about the middle of the
last century.
[31] Rosoman Street was called after Mr. Rosoman, who about
1756 built the west side, which was then called Rosoman Row.
Rosoman, who acted at the New Wells in 1744, was the well-
known proprietor of Sadler’s Wells. Pinks (Clerkenwell) states that
the houses numbered (in his time) 5 to 8 occupied the site of the
Wells.
[32] The New Wells seem to have been already established in
1737. The earliest advertisement quoted in Pinks is of 1738, but
there are earlier advertisements (W. Coll.), May to August 1737,
in one of which reference is made to the alterations in the theatre
that season.
[33] Daily Post, 3 July, 1742 (quoted in Gent. Mag. 1813, pt. ii.
p. 561).
[34] Doran’s London in Jacobite Times, ii. pp. 148, 149.
[35] The English Grotto has escaped the minute research of
Mr. Pinks, and his continuator Mr. Woods (cp. however, Daniel,
Merrie England, i. chap. ii. p. 33). It is practically known only from
the following views:—
(1) A view of the English Grotto, near the New River
Head. Chatelain del. et sculp. 1760. Crace, Cat. p. 591,
No. 60 (cp. engraving (circ. 1760), without artist’s name,
in W. Coll.).
(2) The Grotto, near the New River Head, 1760. A
drawing in Indian ink. Crace, Cat. p. 590, No. 59.
(3) A water-colour copy of No. 1 by R. B.
Schnebellie. Crace, Cat. p. 591, No. 61.
[36] The continuator of Pinks (p. 740) quotes advertisements of
1769, without, however, specifying the newspapers referred to. J.
T. Smith, Book for a Rainy Day, p. 70, refers to the Grotto Garden
as being kept by Jackson in 1779. Pinks (p. 169) mentions the
fountain and Grotto in 1780, and describes the site.
[37] Rockhoutt = Rockholt House in Essex.
[38] The legs referred to are those of Sir Thomas Robinson,
the principal proprietor of Ranelagh, nicknamed Long Sir Thomas.
[39] The New Wells, Clerkenwell.
[40] Cuper’s Gardens, Lambeth.
[41] Newspaper advertisement in “Public Gardens” collection in
Guildhall Library, London.
[42] Advertisement in Daily Advertiser, 8 July, 1745.
[43] Sadler originally advertised the place as “Sadler’s New
Tunbridge Wells,” but it soon became known simply as Sadler’s
Wells. On the confusion with the neighbouring New Tunbridge
Wells (Islington Spa), see Islington Spa, supra, note 3.
[44] About 1800 the forgotten well was accidentally re-
discovered between the stage door and the New River.
[45] A poem by William Garbott, entitled the New River,
published probably about 1725.
[46] A new song on Sadler’s Wells, set by Mr. Brett, 1740.
[47] The Sadler’s Wells anglers are mentioned in the Field Spy,
a poem of 1714. The New River remained open until 1861–62
when it was covered in.
[48] A newspaper cutting in “Public Gardens” collection in
Guildhall Library, records the death on 2 February, 1786, of Mrs.
Bennet, of Merlin’s Cave, Spa Fields, who was the successor of
her uncle, Mr. Hood.
[49] A view of the Merlin’s Cave at Richmond forms the
frontispiece of Gent. Mag. 1735; on the cave, see Walford’s
Greater London, ii. 345, ff
[50] A square stone bearing the inscription given below was,
about 1760, over an old gateway in the wall to the north of the
Long Room, and was still there in 1843. In 1850 it was to be seen
in Coppice Row, now Farringdon Road.
ST
THIS IS BAGNIGGE
HOUSE NEARE
THE PINDER A
WAKEFEILDE
1680.
The Pinder a Wakefielde (the modern representative of which
stands near the old site in Gray’s Inn Road) was a tavern; and
some writers have inferred from the above inscription that
Bagnigge Wells itself was a place of entertainment as early as
1680.
[51] Over one of the chimney-pieces of the room was the garter
of the order of St. George, in relief, and over another the bust of a
woman in Roman dress, popularly supposed to represent Nell
Gwynne. This bust was let into a circular cavity of the wall,
bordered with festoons of fruit and flowers moulded in delft earth
and coloured after nature. Owing to the number of visitors
promenading in the Long Room to the hindrance of the waiters,
the room was, before 1797, divided into two, though we are told
that the “former elegance” remained.
[52] The organ and its organist (under Davis), Charley Griffith,
are shown in an engraving “The Bagnigge Organfist” (undated).
“Published for the benefit of decayed musicians.”
[53] Picture of London, 1802.
[54] “Bagnigge Wells,” a song in the London Magazine, June,
1759.
[55] Colman’s prologue to Garrick’s Bon Ton, 1775.
[56] This is made sufficiently clear in the Sunday Ramble
(1774, &c.); in the poem cited in the next note, and in Trusler’s
London Adviser (1786).
[57] Bagnigge Wells, an anonymous poem (1779).
[58] The life of John Rann, otherwise Sixteen Strings Jack,
reprinted London, 1884; C. Whibley in The New Review, 1896, p.
222; cp. also the print “The Road to Ruin.”
[59] Sale Catalogue, 1813. (Copy in Brit. Mus.)
[60] A few years before 1891, these figures were in the
possession of Dr. Lonsdale of Carlisle (Wheatley’s London P. and
P.).
[61] The temple (behind the Long Room) and the grotto to the
north of it, were, as formerly, in the garden east of the Fleet. The
western garden, previous to its curtailment, contained the rustic
cottage nearly opposite the grotto, and the pond with its swan and
Cupid fountain about the middle of the garden.
[62] For New Year’s day 1751, new fireworks in the Chinese
manner were announced to take place at the Sir John Oldcastle
(Pinks, p. 738). This was a special subscription entertainment.
The regular open-air amusements appear to have come to an end
in 1746.
[63] The Well at Battle Bridge (i.e. St. Chad’s) is mentioned
with four other London Wells in the Macaroni and Theatrical
Magazine for January 1773, p. 162. A Mr. Salter was part
proprietor of the Well for many years previous to 1798. His mind
became deranged and on 17 July, 1798, he was found drowned in
a pond in the garden of St. Chad’s (The Courier for 18 July,
1798).
[64] Coull’s St. Pancras, p. 22.
[65] In the minutes of a Vestry Meeting in St. Giles’s parish,
held in 1676, it is recorded that a meeting is appointed with the
parishioners in St. Andrew’s, Holborn, about the Bowling Green in
Gray’s Inn Fields and the houses near thereabouts built (F.
Miller’s St. Pancras, p. 77).
[66] Malcolm’s Manners and Customs of London (1811), p.
209.
[67] Barras’s advertisement is quoted in Palmer’s St. Pancras,
p. 310.
[68] It was generally known as the Bowling Green House, but
the sign of the inn appears to have been the Three Tuns, for in a
plan of the new road from Paddington to Islington (London Mag.
1756), the place is marked as the Three Tuns Ale House and the
Three Tuns Bowling Green.
[69] Malcolm in Gent. Mag. 1813, pt. 2, pp. 427–429. The
Bowling Green House is marked in Horwood’s Plan C, 1799; in a
map of 1806 in Lambert’s London, vol. iv., and in Wallis’s plan of
1808.
[70] Walford, v. 304, cites a newspaper advertisement of
September 1718, announcing that “there is a strange and
wonderful fruit growing at the Adam and Eve at Tottenham Court,
called a Calabath, which is five feet and a half round, where any
person may see the same gratis.”
[71] Cunningham’s Handbook of London (1850), “Tottenham
Court Road”; see also Paxton’s History of St. Giles’ Hospital and
Parish (cited in F. Miller’s St. Pancras, p. 161), where similar fines
for drinking at Tottenham Court are recorded for the year 1644.
[72] His first ascent was on 15 September, 1784. This was the
first ascent in England, but it may be noted that Mr. J. Tytler had
made an ascent from Edinburgh on 27 August, 1784.
[73] The Morning Herald and Daily Advertiser, Saturday, 14
May, 1785.
[74] See Horwood’s Plan, 1793.
[75] See Wallis’s Plan, 1808.
[76] Thus the grounds must at that time have covered the
space now occupied by Eden Street and Seaton (formerly Henry)
Street.
[77] There may be some exaggeration in this description
(based on Wilkinson), for in the Picture of London, 1802, p. 370,
the Adam and Eve is enumerated among the tea-gardens
frequented by the middle classes, and is described as somewhat
similar to the Jew’s Harp, with a small organ in the room upstairs
where tea, wine and punch are served.
[78] Walford, v. 305.
[79] Stow’s Survey, p. 7 (ed. Thoms).
[80] At a depth of four feet was a bottom of “lettice” work under
which the water was five feet deep.
[81] Watts’s building operations do not appear to have been
completed till about 1811 or later (cp. Hughson’s London, iv.
(1811), p. 414).
[82] Peerless Pool is mentioned in The Picture of London, 1829
(p. 370), as one of the principal public baths of London.
Cunningham, Handbook of London, 1850, speaks of it as a then
existing public bath. Mr. Hyde Clark writing in Notes and Queries
(7th Series, viii. 214, 215) for 14 September, 1889, says that “it
continued to be used as a bath until comparatively late years.” I
am informed that after the death of Joseph Watts, the Bath was
carried on by his widow, Mrs. Watts, and by the sons, Thomas
Watts of the British Museum and his brother. It seems to have
been built over at some time between 1850 and 1860.
[83] The grounds originally extended on the north-east to a
tavern called The Fountain, which was frequented by tea-parties:
—
And there they sit so pleasant and cool,

And see in and out the folks walk about,
And gentlemen angling in Peerless Pool.
(Lines in Hone, loc. cit.). There is now a public house called

The Old Fountain at the east end of Baldwin Street. The
Shepherd and Shepherdess (q.v.) was close by on the other side
of the City Road.
[84] Cp. Lewis’s Islington, p. 31, note 6, referring to August
1758.
[85] For the connexion of the Salvation Army with the Eagle,
and for some details as to the history of the Eagle tavern and
gardens see The Times for 1882 (Palmer’s Index, under
“Salvation Army,” June to September). On the Eagle see also
Dickens, Sketches by Boz (Miss Evans and the Eagle);
Hollingshead’s My Lifetime, i. p. 25, ff.; Ritchie’s Night-side of
London (1858); Stuart and Park, The Variety Stage, p. 35, ff. &c.;
Era Almanack, 1869, p. 80; H. Barton Baker’s The London Stage,
ii. p. 254, ff.; and a view of the garden in Rogers’s Views of
Pleasure Gardens of London, p. 57.
[86] The Post Man, Oct. 3 to 6, 1702, has the advertisement
“At Milend the garden and house called the Jews Spring Garden
is to be let. Enquire at Capt. Bendal’s at Milend” (Notes and
Queries, 1st ser. ii. 463). Mr. Alexander Andrews (ib. 2nd ser. viii.
422) has shown that this Jews’ Spring Garden is in all probability
to be identified with the Spring Garden marked in a map of
Stepney parish of 1702.
[87] Rayner, Master of the Spring Garden at Stepney, died April
3, 1743, aged 70 (London Daily Post for 6 April, 1743).
[88] Low Life (1764), “Stepney Spring Gardens.”
[89] Dodsley’s London (1761), s.v. “Stepney.” There are
modern streets known as Garden Street and Spring Garden
Place, but these are some distance south of the Mile End Road,
not far from St. Dunstan’s, Stepney.
[90] See Crace, Cat., p. 616, No. 80.
[91] “The back entrance was from the fields, beyond which,
north, was a narrow winding passage, with garden palings on
each side, leading into High Street” (Smith’s Book for a Rainy
Day, p. 39).
[92] Pulled down in 1791. Devonshire Mews was built on the
site.
[93] These lines, often erroneously attributed to Lady Mary
Wortley Montagu, occur in Pope’s The Basset-table, an Eclogue.
The allusion in the second line is to Sheffield, Duke of
Buckingham.
[94] Gough issued, 1738–9, silver tickets at 12s. each,
admitting two persons for the season. In 1740 the silver season-
ticket, admitting two, cost £1 1s. There are extant silver (or rather
base silver) season tickets of 1766 (Wilkinson, Londina, vol. ii.,
last plate, No. 19) and of 1767 (Brit. Mus.). These later tickets,
admitting two, cost £1 11s. 6d., or two guineas. There are copper
tickets of 1770 (specimen in Brit. Mus.). In 1774 the ticket for two
cost two guineas.
[95] The use of the old spelling which occurs in all the
advertisements and contemporary notices must be conceded.
[96] J. T. Smith and several modern writers state that Trusler
was proprietor in 1751. It would appear, however, from the
newspapers that in 1754 John Sherratt was proprietor, and in May
1755 Mr. Beard was stated to have “lately taken the Gardens.”
Trusler was undoubtedly manager from 1756–1763. He died
before October 1766.
[97] Cp. Vocal Melody, Book iii. A favourite collection of songs
and dialogues sung by Master Arne and Miss Faulkner at
Marybone Gardens, set by Mr. Arne. Published 15 August, 1751,
by J. Walsh, Catherine Street, Strand.
[98] The name is variously spelt; usually Falkner.
[99] See Trusler’s Memoirs, p. 63, ff.; cp. Dict. Nat. Biog., art.
“Dunk, George Montagu, second Earl of Halifax,” 1716–1771.
[100] The Servant Mistress, a burletta translated from the
Italian. Price 6d., printed at Marybone Gardens.
[101] Hone’s Year Book, pp. 500–503.
[102] Trusler’s Memoirs, p. 57.
[103] Two men were executed 15 June, 1763, at Tyburn for
robbing, in Marybone Fields, the waiters belonging to Marybone
Gardens.
[104] Indenture between Robert Long and Thomas Lowe,
dated 30 August, 1763. The lease was for fourteen years. Trusler
ceased to reside at the Gardens in 1764 when he went to Boyle
Street, Saville Row, and Miss Trusler carried on business as a
confectioner.
[105] The vocalists 1763–1767, besides Lowe, were—1763,
Mrs. Vincent, Mrs. Lampe, Miss Catley, Miss Hyat, Miss Smith,
Miss Plenius (1763?), and Mr. Squibb (Sig. Storace and Miss
Catley had benefits); 1764, Mrs. Vincent, Mrs. Lampe, Miss
Moyse, Miss Hyat, Mr. Squibb; 1765, Mrs. Vincent, Mrs. Collett,
Miss Davis, Mrs. Taylor, Mr. Legg; 1766, Mr. Taylor, Mr. Raworth,
Mrs. Vincent, Miss Davis; 1767, Mrs. Gibbons.
[106] The vocalists in 1768 were Reynoldson, Taylor, Phillips,
Miss Davis, Miss Froud.
[107] Performers in 1769: Pinto, leader; Hook; Park, hautboy.
Vocalists, Mrs. Forbes, Miss Brent, Mr. Herryman, Mr.
Reynoldson.
[108] Performers, 1770: Barthelemon (violin); Hook; Reinhold,
Charles Bannister; Mrs. Thompson; Mrs. Barthelemon; Mrs.
Dorman. It is well known that Thomas Chatterton the poet wrote a
burletta called The Revenge, which he sold to the management of
Marybone Gardens for five guineas. It was not published till 1795,
when it was issued as The Revenge, a burletta acted at
Marybone Gardens, MDCCLXX. In the Marybone Gardens’
advertisements of 1770 (and of later dates) no burletta bearing
the name of The Revenge appears, and the writer of the article
“Chatterton” in Dict. Nat. Biog. thinks that the burletta must have
been performed at some time subsequent to 1770, the year of
Chatterton’s death. In The Revenge as published, the dramatis
personæ are Jupiter, Mr. Reinhold; Bacchus, Mr. Bannister;
Cupid, Master Cheney; Juno, Mrs. Thompson. Reinhold,
Bannister, and Mrs. Thompson sang at the Gardens 1770–1773,
and Cheney in 1770. I may add that a burletta called The
Madman, performed at the Gardens in 1770, has a plot quite
distinct from that of The Revenge.
[109] Performers, 1771: Hook; solo violin, Mons. Reeves;
Charles Bannister; Mrs. Thompson; Miss Esser; Miss Harper
(afterwards Mrs. John Bannister); Miss Thomas; and Miss Catley
who sang “The Soldier tired of War’s Alarms”; “Sweet Echo,” from
Comus (the echo “sung by a young gentleman”), &c.
[110] According to J. T. Smith (Rainy Day, p. 52, n.), Torré was
a print-seller in partnership with Mr. Thane, and lived in Market
Lane, Haymarket. Other fireworkers at the Gardens at this period
were Clitherow (1772); Clanfield (1772 and 1773); Caillot of
Ranelagh (1773, 1775, 1776).
[111] Performers, 1772: Hook, organ; Charles Bannister,
Culver, Reinhold, Mrs. Calvert, Mrs. Forbes, Mrs. Foster, Mrs.
Cartwright and Mrs. Thompson.
[112] On his own benefit night in July 1772, Torré gave a
representation of Hercules delivering Theseus from Hell, in
addition to the Forge of Vulcan.
[113] Performers, 1773: Charles Bannister; Reinhold; Phillips;
Barthelemon (leader); Miss Wilde; Mrs. Thompson; Mrs.
Barthelemon. “Mr. Dibdin, of Drury Lane Theatre,” was
announced to sing in Barthelemon’s “La Zingara, or the Gipsy” on
Barthelemon’s benefit night.
[114] Also on 13 June, 1774.
[115] Performers, 1774: Fisher (violin), Dubellamy, Reinhold;
Mons. Rodell, “musician to the King of Portugal,” German flute;
Miss Wewitzer, Miss Trelawny, Miss Wilde.
[116] A large printed bill referring to this entertainment is in the
possession of Mr. H. A. Rogers, and is reproduced in his Views of
Pleasure Gardens of London, p. 30.
[117] Nollekens, i. 33, chap. ii.
[118] At a bazaar held in the Portman Rooms, Baker Street, in
1887 (Nov. 22–26), for the benefit of the charities of Marylebone
Church, an ingenious reproduction was attempted, under the
direction of Mr. Thomas Harris, the architect, of the latticed
alcoves, lamp-hung trees, &c., of the old Marybone Gardens (see
A Booke of ye olde Marybone Gardens, 1887 (sold at the bazaar);
Daily Telegraph for 23 November, 1887).
[119] An account of the robbery and murder in 1808 of Mr.
William Joachim in the Marylebone Fields mentions that he was
on his way home to Lisson Grove, after a visit to the Jew’s Harp
Tavern to see the skittle-playing (F. Miller’s St. Pancras, p. 238).
[120] Wheatley, London Past and Present, s.v. “Yorkshire
Stingo,” states on the authority of Cooke’s Old London Bridge, p.
7, that a bridge designed by the celebrated Thomas Paine, being
the second cast-iron bridge ever constructed, was brought to
London in 1790 and set up in the bowling-green of the Yorkshire
Stingo; it was afterwards taken back to Rotherham (where it had
been made in 1789) and broken up in 1791.
[121] The Picture of London, 1802, p. 370, mentions the
Yorkshire Stingo as a house many years celebrated for rustic
sports on May Day.
[122] Newspaper cuttings in W. Coll.; cp. Hollingshead’s My
Lifetime, i. 24, and see also Stuart and Park, The Variety Stage,
p. 38, who mention Cave and Glindon as the comic vocalists. The
saloon, which was in the rear of the tavern, had a small but
capable orchestra directed by Love, afterwards leader at the
Princess’s Theatre under Charles Kean. Miss Tunstall of Vauxhall
was at one time a singer there.
[123] Pulled down about 1895.
[124] Woodward’s Eccentric Excursions, p. 18.
[125] Before 1702.
[126] The Country Journal, or the Craftsman, 7 March, 1729–
30. If an allusion in a pamphlet of 1735—A seasonable
examination of the pleas and pretensions of ... Playhouses
erected in defiance of Royal Licence (London, printed for T.
Cooper, 1735)—may be relied on, Pancras Wells had about that
time some kind of (unlicensed) theatrical or “variety”
entertainments resembling those of Sadler’s Wells.
[127] According to Roffe (St. Pancras), Pancras Wells
occupied the south side of Church Hill from its base to its summit.
Palmer in his St. Pancras, published in 1870, says the Well “is
now enclosed in the garden of a private house, neglected and
passed out of mind.”
[128] It is shown in the bird’s-eye view of Pancras Wells of
1730. In April 1731, James Dalton, a notorious footpad, robbed a
linenpedlar at night near the Adam and Eve after drinking with
him at the tavern (Pinks’s Clerkenwell, p. 549).
[129] The Connoisseur, 1754, No. 26.
[130] Five of these pier-glasses were stolen from the long room
in 1778 (London Evening Post, 11–14 July, 1778).
[131] Advertisement of 1786 quoted in Clinch’s Marylebone
and St. Pancras, p. 157.
[132] There are advertisements of the Adam and Eve issued
(at the end of the eighteenth and beginning of the nineteenth
century?) by G. Swinnerton, Junr. and Co., and by George
Lambert (quoted in Walford, vol. v. p. 338). The Picture of
London, 1805, mentions the Adam and Eve Tea-gardens,
bowling-green, &c., but the conversion of the gardens into the
cemetery (authorised by Act of Parliament in 1803) appears to
have been already carried out in 1804.
[133] There is a mention of the inn in 1725: the Assembly
Rooms were certainly in existence in 1750, and perhaps at an
earlier date. The original sign of the inn appears to have been the
Black Bull; see Notes and Queries, 1st ser. viii. p. 293; W. Elliot’s
Some Account of Kentish Town (1821), p. 65.
[134] The new or altered building contained the circular
structure shown in so many views of the place.
[135] The White Conduit meadow long continued in use as a
cricket ground. About 1784 and subsequently a club composed of
gentlemen and men of rank played its matches there. Among the
players were the Duke of Dorset, Lord Winchilsea, Lord Talbot,
Col. Tarleton, and Thomas Lord, who afterwards established the
Marylebone Cricket Club.
[136] A poem by W. W[oty] printed in the London Chronicle,
1760, vol. vii. p. 531.
[137] “White Conduit Loaves” was a London cry till about 1825.
[138] Forster’s Life of Goldsmith; cp. Goldsmith’s Citizen of the
World, Letter 122.
[139] “An Awkward Position,” a painting by A. Solomon, depicts
the situation. This was exhibited in the Royal Academy, and
reproduced in the Illustrated London News, 14 June, 1851.
[140] Ashton, The Fleet, p. 66.
[141] Bartholomew sold his interest in White Conduit House 25
March, 1795.
[142] About 1772 these performances were prohibited on
Sundays.
[143] See a bill in the London Sections Collection, Guildhall
Library, and cp. Rogers’s Views of Pleasure Gardens of London,
p. 55; also G. Cruikshank’s Ivan Ivanitz Chabert, a print published
13 March, 1818. Hone’s Every Day Book, ii. p. 771, ff.
[144] Born 1769, died 1838.
[145] Till May of 1829 the old building was still standing.
[146] Hone’s Every Day Book, ii. p. 1204.
[147] Cp. the White Conduit concert described in the Sketches
by Boz (“The Mistaken Milliner,” cap. viii.).
[148] The Variety Stage, by Stuart and Park, p. 8; 103.
[149] The place appears to be referred to as early as 1633 as
“the bowling place in Islington Fields” (Pinks, p. 710).
[150] Mrs. Dobney died at about the age of ninety on 15 March,
1760.
[151] Pinks states that Price had been starring at the Three
Hats, Islington, prior to his performance at Dobney’s in 1767 (cp.
Memoirs of J. de Castro (1824), p. 29, who says that Price,
Thomas Johnson, and old Sampson exhibited at the Three Hats).
This may have been the case, though from 1758 to the spring of
1767, Thomas Johnson was certainly the chief equestrian
performer at the “Three Hats.”
[152] London Evening Post, August 1776. The Pantheon is the
tea-house in Exmouth Street.
[153] Tomlins in his Perambulation of Islington, published in
1858, but written in part about 1849, describes Prospect House
as still existing behind Winchester Place, though the bowling
green (he says) had been already covered by Winchester Place.
[154] Busby’s Folly is first mentioned in 1664 as a meeting-
place of the Society of Bull Feathers Hall, a fraternity of Odd
Fellows. It is supposed to have derived its name from Christopher
Busby, landlord of the White Lion Inn, Islington, in 1668.
[155] Prologue written and spoken by Mr. Gibson before the
Orphan at the New Theatre in the Haymarket on 31 May, 1762
(Owen’s Weekly Chronicle or Universal Journal, June 5 to 12,
1762). The “wonder of a Chelsea field” mentioned in this prologue
is evidently Coan, the dwarf (called “the jovial pigmy”), who
attracted visitors to the Dwarf’s Tavern in Chelsea Fields (see
infra, Star and Garter, Chelsea).
[156] According to Nelson and Lewis, the house facing to the
south at the northern termination of Colebrooke Row, was
occupied about 1772 by the Rev. John Rule, who there kept a
school, of some repute, for gentlemen’s sons. The Castle Inn was
the adjoining house and a house next to the Castle was supposed
by a doubtful tradition (cp. J. Knight, art. “Cibber” in Dict. Nat.
Biog.) to be that in which Colley Cibber died 12 December, 1757
(see Nelson and Lewis). The old house with a red-tiled roof, still
existing, though divided into the dwelling houses Nos. 56 and 57
Colebrooke Row, was apparently the Castle Inn. The southern
end of Colebrooke Row was built in the present century. The Row
also now extends a little farther to the north than when Nelson
wrote, so that Rule’s house is not now at the extreme northern
end of the Row.
[157] Sampson’s Riding School at Islington is mentioned in the
Macaroni and Theatrical Magazine for January 1773, p. 162,
together with Astley’s and Hughes’s.
[158] They were probably in existence before this date, but are
not marked in the survey of Islington of 1735. An advertisement in
The Morning Herald of 22 April, 1786, announces the sale of the
ground-rents of an Islington copyhold estate. This estate, situated
“in the Lower Street, opposite Cross Street, Islington, and
extending down to Frog Lane,” comprised a brick mansion and
garden, four dwelling-houses and gardens, and the Barley Mow
Tea House and Gardens. A plan of the estate was to be seen at
Mr. Spurrier’s, the auctioneer’s, Copthall Court, Throgmorton
Street. The estate was therefore between the present Essex
Road, where it is touched by Cross Street, and Popham Road.
[159] See the survey of roads in Islington parish in 1735
(Nelson’s Islington, p. 20).
[160] Hone, Every Day Book, i. p. 860. Tomlins (Islington, 204,
205) discovered that in 1753 it was occupied by a currier, and
supposes, therefore, that it was not a place of entertainment till
after that date. The meeting of the Highbury Society there before
1740 seems however to bear out Hone’s assertion that
Copenhagen House was already an inn in the first half of the
eighteenth century.
[161] Map in Gibson’s edition of Camden’s Britannia, 1695.
[162] Hone, however, shows (op. cit. 860) that there is some
reason for supposing that Copenhagen House was not in
existence until after 1624.
[163] On the Highbury Society, see note infra under Highbury
Barn.
[164] The graphic account in Hone (op. cit. 862) is worth
reading, though too long for quotation here.
[165] Hazlitt’s memoir is published in the Examiner for
February 17, 1819; most of it is reprinted in Hone’s Every Day
Book, i. 865, ff.
[166] Picture of London, 1823 and 1829; Hone’s Every Day
Book, i. 859, 870.
[167] The hay-harvest is referred to in Nelson’s Islington, 1811,
74. A view of 1809, published by Cundee in the Juvenile Tourist,
1810, shows cockney visitors playing in the hay.
[168] Plan in Lewis’s Islington.
[169] J. Hollingshead’s My Lifetime, i. 13. The cricket ground
was between Copenhagen House and Maiden Lane.
[170] Tomlins, Perambulation of Islington, p. 205.
[171] F. Miller, St. Pancras, 269.
[172] Highbury Barn, i.e., the grange or farm of Highbury
Manor, is mentioned by that name at an early period, and there
are extant various leases of it of the fifteenth century, granted by
the Prior and Convent of St. John of Jerusalem (e.g. “our certain
grange, situate upon the site of our manor of Highbury called
Highbury Barn”—see Tomlins’s Perambulation of Islington). The
name Highbury Barn is, therefore, much older than the date of the
incorporation of the large barn of Highbury Farm with the
Highbury Tavern premises.
[173] The site of the Prior’s house was occupied by a private
residence called Highbury House built in 1781 and immediately
opposite the Highbury Barn Tavern.
[174] The Highbury Society, formed by Protestant Dissenters to
commemorate the abandonment of the Schism Bill at the end of
the reign of Anne, met at first at Copenhagen House, but about
1740 assembled at Highbury Barn. The members beguiled their
pilgrimage from Moorfields to Highbury by bowling a ball of ivory
at objects in their path. This society was dissolved about 1833.
[175] The younger Willoughby was certainly proprietor in 1792
and later, and Lewis says he succeeded his father on the death of
the latter in December 1785. In May 1789 Highbury House
(Nichols, Canonbury, p. 31, note) opposite the Tavern was sold by
auction, as were also Highbury Tea House with gardens and
bowling-green and two good messuages adjoining, together with
many fields in the neighbourhood. This sale does not, however,
necessarily imply any change in the management of Highbury
Barn, which may at that time have been only rented by
Willoughby from the owner of Highbury House and the adjoining
property.
[176] A few years previous to 1811 Willoughby cultivated at
one end of the gardens a small plantation of hops, and afterwards
erected a brewery on the premises. Highbury Barn was
sometimes called “Willoughby’s Tea Gardens” (Picture of London,
1802).
[177] Lysons, Nelson and Lewis all identify the moated house
called in the Survey of 1611 “The Devil’s House” or the “Lower
House” with the old Tallington or Tollington Manor House. In the
survey of the roads of Islington (Nelson’s Islington, p. 20),
however, both Tallington House and Devil’s House are separately
marked, the two being divided by Heame Lane, a lane running at
right angles to Tallington (Devil’s) Lane. This Tallington House
must therefore have been an eighteenth-century residence and
not the old Manor House.
[178] Nelson (Islington), writing about 1811, says that about
thirty or forty years before his time (1776?) the landlord’s name
was Fawcett.
[179] This seems to be implied by Nelson (Islington, 1811),
who says that in his time the old “house had been fitted up in the
modern taste.”
[180] Lewis’s Islington, 1841, mentions the house as still
existing, and it is described as still standing in Tomlins’s
Perambulation of Islington, a work published in 1858, but in part
written nine years before the date of publication.
[181] Tea-drinking on Sunday at Little Hornsey is mentioned in
the Connoisseur, No. 68, May 15, 1755, and Hornsey Wood is
referred to in The Idler, No. 15, July 1758, in a way which implies
that its reputation as a place of Sunday recreation was already
well established. It appears from a passage in Low Life, referred
to in the next note, that in or before 1764 the sign of the tavern
was The Horns. The place was, however, usually known as
Hornsey Wood House, and in its latest days as Hornsey Wood
Tavern.
[182] Low Life (1764), p. 46.
[183] Mr. Rose, the “citizen at Vauxhall,” described in the
Connoisseur, May 1755, No. 68, used to grumble when his wife
and daughters went “to Little Hornsey to drink tea.”
[184] Newspaper cutting, 1753 (W. Coll.).
[185] See Boyne’s Trade Tokens, ed. Williamson, ii. p. 818.
This token is undated. The only dated token of Hampstead is one
of 1670.
[186] The “Mirmillo” of Garth’s Dispensary.
[187] The modern public-house in Well Walk called the Wells
Tavern, though at one period, (before 1840) bearing the sign of
the Green Man, is probably on the site of the original tavern.
[188] Sion Chapel (the exact site of which is unknown) is of
course distinct from the Episcopal Chapel into which the Great
Room was converted in 1733.
[189] Baker’s comedy, Hampstead Heath, London, 1706.
[190] The Country Journal, or the Craftsman for 16 October,
1736, has the notice:—“On Sunday between seven and eight in
the evening one Mr. Thomas Lane, a farrier of Hampstead, going
home from the Spaniards upon the Heath near the house called
Mother Huff’s,” was attacked and robbed and stripped naked by
three men who jumped out of the bushes.
[191] Lysons’s Magna Britannia, vol. iii. 1724, p. 44.
[192] This lady had made an earlier appearance at Cuper’s
Gardens; see Welsted’s Epistle on False Fame.
[193] The spring at this time was adjacent to the Great Room,
and was in this position, i.e. on the opposite side to the existing
fountain, at any rate as late as 1806.
[194] In Bickham’s Musical Entertainer (1733, &c.).
[195] Evelina (1778), letter li.
[196] The house, No. 17 in Well Walk, which is just behind the
existing fountain, has a shallow well supposed to contain the
source of the original spring.
[197] MS. History of Middlesex, 1752, quoted by Park.
[198] A Modern Sabbath, 1797, p. 53; see also Woodward’s
Eccentric Excursions, 13.
[199] Dickens, Pickwick Papers, cap. xlvi.
[200] Cp. The Idler, No. 15, July 1758.
[201] Lysons, Environs, ii. 527.
[202] Evelyn (Diary, 2 June, 1676) describes the gardens as
very large and woody, but ill kept.
[203] E.g. “Galloway Races” in 1725 and 1729.
[204] Ambulator, 1774; Dodsley’s London, 1761.
[205] From the manuscript history of Middlesex quoted by Park
(Hampstead), the spring would appear to have been discovered
about 1742; the date on the reservoir containing the water was,
however, 1714, and Walford (v. 245) states that the spring was
known before 1600. But there is no evidence that Kilburn Wells
was a place of entertainment earlier than about 1742, though the
Bell tavern dated from about 1600.
[206] Richard Owen Cambridge, Dialogue between a master
and his servant (1752). “Kupers” = Cuper’s Gardens, Lambeth.
[207] Picture of London, 1802 and 1829.
[208] Gibson, View of the Gardens near London, Dec. 1691.
[209] Lord Ranelagh’s house remained standing till 1805, and
was used in connexion with the Ranelagh entertainments.
[210] Robinson lived at Prospect Place adjoining the gardens.
He died on 3 March, 1777.
[211] Cp. Walpole’s letter to Mann of 26 May, 1742: “The
building and disposition of the gardens cost sixteen thousand
pounds.”
[212] Walpole to Mann, 26 May, 1742.
[213] Walpole to Conway, 29 June, 1744.
[214] Walpole to Montagu, 26 May, 1748.
[215] Gray to Chute, July 1745 (Gray’s Works, ed. Gosse, ii.
125, ff.).
[216] Works, ed. Gosse, ii. 139.
[217] See especially Kearsley’s Strangers’ Guide (1793?).
[218] This was the number about 1793.
[219] Burney says that the first organist was Keeble, who was
succeeded by Butler. Burney himself was organist in 1770.
[220] Boswell, Life, chap. xxvi. p. 236, ed. Croker.
[221] Life, 1777–1778, chap. lxi. p. 561, ed. Croker.
[222] In the early days, sometimes one shilling and two
shillings, including the breakfast and the morning concert. On
special nights when fireworks were displayed, the price was
raised to three shillings or more. Tickets costing from half a
guinea to two guineas were issued for the masquerades.
[223] Sometimes it was advertised as open “every evening.”
People were allowed to walk in the gardens and view the Rotunda
during the day-time for one shilling.
[224] “Harlequin in Ranelagh,” London Magazine, May 1774.
[225] Cp. Gent. Mag. 1764, p. 247.
[226] Ranelagh House: a satire, 1747.
[227] London Magazine, 1774.
[228] Other early vocalists were:—Mrs. Storer (1751); Miss
Young (1755); Miss Formantel (Ten favourite songs sung by Miss
Formantel at Ranelagh, music by Mr. Oswald, published July
1758).
[229] According to a statement of Burney’s (note in Croker’s
ed. of Boswell’s Johnson, p. 143, anno “1763”), the salt-box song
was sung by Beard accompanied on that instrument by Brent, the
fencing master, while Skeggs played on the broomstick as
bassoon. Croker assigns the composition, and apparently the first
performance, of the Ode to 1769, and states that the first edition
(which he himself had seen) of it bears the date 1749, a date
which he considered to be a misprint for 1769. But the date 1769
is, as some later writers have seen, clearly erroneous, and the
composition—and possibly the first performance at Ranelagh—
must be assigned to 1759. The published edition of the Ode, in
the British Museum, is dated (May) 1763, and the Ode was
undoubtedly performed at Ranelagh on 10 June of that year
(1763). (See Annual Register; Lloyd’s Evening Post, 8–16 June,
1763.)
[230] Cp. Six new English songs composed by Ferdinando
Tenducci, and to be sung by him at Ranelagh. Sold by the author
at his lodging in the Great Piazza, Covent Garden, 1763 (W.
Coll.).
Other performers at this period were:—1762: Champness,
Hudson, Miss Thomas, Miss Brent. 1763: Dearle, Miss Wright,
Miss Brent. 1765 (?): the elder Fawcett.
[231] Gent. Mag. 1767, p. 277.
[232] Walpole’s Letters, ed. Cunningham, ii. 150, ff. (Walpole to
Mann, 3 May, 1749).
[233] It is to be feared that this advertisement was an invention
of the editor’s, but it would have had little point for his readers had
it not been actually based on familiar incidents of the Ranelagh
masquerades.
[234] Mrs. Baddeley also sang there in 1772.
[235] An impetus to the fireworks seems to have been first
given by Angelo, father of Henry Angelo, who directed the
displays in 1766. In 1771 the fireworkers were Clitherow and
Caillot.
[236] The admission ticket for the Regatta Ball (Lake scene)
was prepared by Cipriani and Bartolozzi.
[237] Evening Mail, Feb. 15–17, 1792.
[238] Newspaper cutting [W. Coll.] assigned to 28 June
(referring to 27 June), 1793. Mr. Vizetelly (Chevalier D’Eon, p.
322) states that D’Eon fenced at Ranelagh in 1794. The
managers of Ranelagh had given the Chevalier, who was then in
money difficulties, a benefit night in 1791 (24 June).
[239] Another great fête of this period (June 1802 or 1803?)
was the Ball given by the Spanish Ambassador.
[240] The European Magazine, October 1802, and several
newspapers of the time.
[241] The name was spelt Strumbels, Strombels and
Strumbello. Davis (Knightsbridge) calls it Stromboli House.
[242] O’Keefe’s Recollections.
[243] Davis’s Knightsbridge. Strumbelo is marked in the map of
1789 in Fores’s New Guide.
[244] The Star and Garter was at the end of Five Fields Row. In
Faulkner’s time (Chelsea, ii. p. 354), about 1829, the house, no
longer used as a tavern, was Mr. Homden’s Academy.
[245] On the Cherokee Chiefs, see Forster’s Goldsmith, bk. iii.
chap. vi. (ann. 1762).
[246] John Coan, “the unparalleled Norfolk Dwarf,” died there
16 March 1764 (Daily Advertiser, 17 March, 1764).
[247] The Dwarf’s Tavern according to Faulkner (Chelsea, ii.
354), was situated in Chelsea Fields “on the spot which was
afterwards called Spring Gardens, between Ebury Street and
Belgrave Terrace,” and which was subsequently (a few years
before 1829) occupied by Ackerman’s Waterproof Cloth
Manufactory. This Spring Garden is the place usually marked in
the maps (e.g., Horwood’s Plan, B. 1795) as the New Spring
Gardens, Chelsea, and was a place of public entertainment, as
may be inferred from a newspaper advertisement of January
1792: “J. Louis, of New Spring Gardens, Chelsea, having fitted up
likewise the above house (i.e. York Coffee House) in Norris
Street, Haymarket, for the winter, serves dinners and suppers
there.”
This Spring Garden was distinct from the Spring Gardens,
Knightsbridge, a place frequented by Pepys, and perhaps
identical with the World’s End, Knightsbridge (see Davis’s
Knightsbridge, p. 149, ff.). The Knightsbridge Spring Gardens
(which stood about where William Street joins Lowndes Square)
ceased to be a place of entertainment before 1773, in which year
the house belonging to them was occupied by Dr. C. Kelly, who
had his anatomical museum there. Walford (v. 18) engraves from
a drawing in the Crace Collection a view of the “Spring Gardens,”
which he assigns to the Knightsbridge Spring Gardens, but it is
possibly a representation of the Chelsea Spring Gardens.
[248] O’Keefe’s Recollections, vol. i. p. 88: “1762. At Cromwell
House, Brompton, once the seat of Oliver, was also a tea-garden
concert.”
[249] The price appears on the (undated) pewter and brass
admission tickets to Cromwell’s Gardens. The British Museum
has four specimens in pewter, with Cromwell’s head; and one of
the brass tickets.
[250] The Sunday Rambler visits the gardens between 7.30
and 9 p.m.
[251] I follow the Modern Sabbath, ed. 1797, in stating that
Cromwell’s Gardens were identical with the Florida Gardens. In
the second edition of the Sunday Ramble (1776) Cromwell’s
Gardens at Brompton are described under that name, and in the
1797 ed. (A Modern Sabbath) almost the same description is
repeated, and it is expressly stated that the name of the place
had been changed from Cromwell’s to Florida Gardens. On the
other hand, Faulkner describes the Florida Gardens as having
been originally a nursery garden kept by “Hyam” (he is called
Hiem in the advertisements) and converted by him (for the first
time, it is implied) into a place of public amusement. Faulkner
after describing Hale House, mentions Cromwell’s Gardens as a
separate place of amusement earlier than the Florida Gardens.
The contemporary authority of the Modern Sabbath seems,
however, preferable; especially as Faulkner does not appear to
be able to state the precise site of Cromwell’s Gardens. A further
complication may perhaps be thought to be introduced by the
passage in O’Keefe (cited in Note 1) where Cromwell’s Gardens
are described as “at Cromwell House” (i.e. Hale House). But the
inhabitants of Cromwell House from 1754 to 1794, or later, are
well known to have been people of substance, and the gardens
proper of Hale House could hardly have been employed as a tea-
garden. The Florida Gardens (afterwards occupied by Canning’s
Gloucester Lodge) were (as stated above) adjacent to Hale
House, and may possibly at one time have belonged to its
owners, and have been let out partly as a tea-garden and partly
as a nursery. The writer of the Modern Sabbath in fact remarks
that Cromwell’s Gardens is supposed to have taken its name from
the ground being formerly the patrimonial estate of the Protector
who once had a palace here upon the site of which is a
handsome seat (i.e. Hale House). The change of name from
Cromwell to Florida took place (as appears from the various
editions of a Sunday Ramble) at some time between 1776 and
1797. I suggest that the change took place about 1780, because
Lysons (who, however, does not mention Cromwell’s Gardens)
says that the place was “much puffed in the daily papers between
the years 1780 and 1790 by the name of Florida Gardens.” In any
case they certainly were advertised by Hiem as the Florida
Gardens as early as 1781.
[252] The Florida Gardens are described as a place of
entertainment in the Modern Sabbath, published in 1797, but they
were already in the possession of the Duchess of Gloucester in
September 1797. Cp. a newspaper paragraph of 25 September,
1797, in “Public Gardens” Collection in Guildhall Library: “Florida
Gardens, at present in the possession of the Duchess of
Gloucester, were fitted up in an elegant manner as a place of
resort by the late Mr. Wilder [a successor of Hiem?] but did not
answer the purpose for which they were intended.”
[253] These checks in copper and lead resemble the
tradesmen’s halfpenny tokens of the end of the eighteenth
century, and are usually described as tokens: see descriptions in
Sharpe’s Catalogue, p. 89; Atkins, p. 193. Miss Banks, in the MS.
catalogue of her tokens (p. 210) now in the Department of Coins,
British Museum, says respecting the leaden check: “One shilling
was paid on going in, and this ticket given in exchange which
would count for sixpence if the person chose liquor.”
[254] Smith’s Book for a Rainy Day: the description strictly
applies to the year 1795; A Modern Sabbath, chap. ix. (1797),
implies that the place was more refined than Smith’s description
would suggest.
[255] Blewitt lived in Bermondsey Square, where he died in
1805.
[256] Cp. “X” in The Musical Times for October 1, 1893, p. 588.
[257] It is possibly worth while to record the names of some of
the forgotten performers at Bermondsey Spa. Circ. 1785–1788
the vocalists were Mr. Birkett, Mr. C. Blewitt, Mr. Burling (or
Birling), Mr. Harriss; Mrs. Thompson, Mrs. Byrn, Mrs. Piercy; Miss
Stephenson, Miss Pay, Miss Cemmitt; Mme. Floranze. In 1792
the leader of the band was Mr. Peile, and the vocalists were Mr.
Burton, Mr. Milward, Mrs. Freeman, and Mrs. Peile.
Among the burlettas (1785–1788) were “The Quack Doctor,”
“The Fop,” and “The Auctioneer.”
[258] The fireworks in 1792 were by Rossi and Tessier, of
Ranelagh. On 25 September, 1792, “by particular desire, the
Battle of the Fiery Dragons, and the line comet to come from the
Rock of Gibraltar and cause the Dragons to engage.”
[259] This entertainment was probably first introduced in 1786,
in which year (2 September) the Public Advertiser announces “the
representation of the storming of a fort which with the fortifications
cover (sic) 3 acres of ground, the rock being fifty feet high and
200 feet long.” From about 1789 to 1792 it was advertised as a
representation of the Siege of Gibraltar. The writer of A Modern
Sabbath (1797) gives further details. “On the north-east side of
the gardens is a very fine lawn consisting of about three acres,
and in a field parted from this lawn by a sunk fence is a building
with turrets, resembling a fortress or castle.” At each side of this
fortress at unequal distances were two buildings, from which on
public nights bombshells, &c., were thrown. The fire was returned
and the whole exhibited the “picturesque prospect of a siege.”
[260] Gent. Mag. 1800, pt. i. p. 284. Keyse’s house was a large
wooden-fronted building, consisting of square divisions in
imitation of scantlings of stone (J. T. Smith). The entrance to the
Gardens was next to the house, beneath a semi-circular awning.
[261] Hughson’s London, vol. v. (1808), p. 60. The Picture of
London for 1802 mentions in the “Almanack of Pleasures” under
July 17, “A silver cup run for at Spa Gardens, Bermondsey, by
gentlemen’s ponies.”
[262] Blanchard in Era Almanack, 1870, p. 18 (followed by
Walford). Brayley and Mantell (Surrey, iii. 200, 201) say the
Gardens were closed about 1805. Lambert in his London (iv. 140)
published in 1806, speaks of the Spa as still open, but the
passage may have been written a year or more before the date of
publication.
[263] Picture of London, eds. 1802, 1829; Tallis’s Illustrated
London, ed. Gaspey.
[264] In the Era Almanack, 1871, p. 6, it is stated that the
gardens “disappeared in 1869.” Walford, vi. 138, says they
ceased to exist in 1881.
[265] “The principal site of Finch’s Grotto Gardens appears to
have been a triangular piece of ground forming the western side
of St. George’s Street, Southwark, and bounded on the south by
the road called Dirty Lane and on the north by a vinegar yard in
Lombard Street, and the extremity of St. Saviour’s Parish.”
Wilkinson, Londina. A way from Falcon Stairs through Bandy Leg
Walk (now Guildford Street) led directly to the place, and
Williams, Finch’s successor, made an entrance from St. George’s
Fields. Those who came by water landed at Mason’s Stairs.
[266] Goldsmith’s She Stoops to Conquer, act. ii.
[267] The Dukes of York and Gloucester, brothers of George
III., are, however, said to have visited the gardens many times.
[268] List of performers under Finch and Williams:—Messrs.
Oldfield (or Offield?, 1765), Lauder, Dearle, Baker, Barnshaw of
Covent Garden Theatre, Moore, Tom Lowe, Kear (sang at
Marylebone 1754, and at Sadler’s Wells in 1771 and later),
Nepecker, Clarke, Thomas and A. Smith from the Richmond
Theatre, Weston from Drury Lane (1772), Aitken and Murphin,
Master Adams, Master Suett (in 1771, from Ranelagh, supposed
to be Dick Suett the actor), Master Green, and Master Lyon. The
female singers were Mrs. Forbes, Reed, Smith, Taylor, Clark, and
Dorman, and Misses Garvey, Thomas (in August 1765), Carli,
Moyse, Snow, Dowson (sang at Sadler’s Wells 1775), Cantrell,
Marshall, and Oakes. The instrumentalists included Cocklin and
Smart, violins; Hudson, organ; Palmer, flute.
[269] “Linco’s Travels” was also performed at the Patagonian
Theatre, Exeter Change. Humphreys’s Memoirs of Decastro, 237.
[270] A programme of a benefit night for 12 September, 1771
(under Williams), may be inserted as a specimen:—
“Act i.—An Overture. A favourite song from the opera of
Pharnaces: ‘Swift wing’d vengeance nerves my arm,’ by Mr. A.
Smith, set by Mr. Bates. A favourite Scotch air by Miss Dowson,
words and music by Mr. A. Smith. An overture by Abel. The Act to
conclude with a celebrated song from Anacreon, set by Mr.
Starling [Sterling?] Goodwin, by Mr. A. Smith. Act ii.—‘The soldier
tired of war’s alarm,’ by Miss Dowson. A new song, ‘O what a
charming thing is a battle,’ by Mr. Barnshaw. An overture in Otho,
Handel. ‘Sweet Echo,’ by a young gentleman from Italy. Trumpet
Concerto by Master Green, pupil of Mr. Jones. The celebrated
song of the ‘British Wives,’ by Mr. A. Smith. A new song by Miss
Dowson. Concerto on the violin by Mr. Smart. The Act to conclude
with ‘Russel’s triumph,’ by Mr. A. Smith, by particular desire. To
which will be added an entertainment called ‘The Gamester,’ to be
sung by Mr. A. Smith, Mr. Barnshaw, Miss Dowson, and Mrs.
Dorman, with a hornpipe in the character of a sailor, by Mr.
Rawlins from the Opera House in the Haymarket. At the end of
the hornpipe Mr. A. Smith will sing the celebrated song of ‘The
storm or the danger of the sea,’ in character. After which will be
displayed a Grand Transparent Painting.”
[271] In 1827 this stone was used as a step in the yard of the
house of a Mrs. Stevens near the site of the Gardens, the verses
being then almost illegible (Wilkinson).
[272] Nichols’s Lambeth, 1786 (in vol. ii. of Bibl. Topog. Brit. p.
77, ff.); Michaelis’s Ancient Marbles in Great Britain, 35–37.
[273] Prologue to Mrs. Centlivre’s Busybody.
[274] Chappell (Popular Music in the Olden Time, ii. 727, 728)
gives words and music.
[275] The gardens were closed on the Sundays of 1752.
[276] Gent. Mag. 1740, 525.
[277] Walpole’s Letters, ed. Cunningham, ii. 32, 24 June, 1746.
Bad company was not unknown in the earlier days of the
gardens: see Welsted’s Epistle on False Fame, 1732:—
“For Cupid’s Bowers she hires the willing scull ...

While here a ’prentice, there a captain bites.”
[278] The Complete Letter-writer, Edinburgh, 1773, quoted in

Notes and Queries, 7th ser. ii. 469.
[279] Twelve songs by Lewis Granom, as sung at Cuper’s
Gardens by Miss Maria Bennett, published London, 24
November, 1752.
[280] The fireworks at Cuper’s in 1751 are described in the
London Daily Advertiser for 10 September, 1751.
[281] ‘The Inspector,’ No. 448, in the London Daily Advertiser
for 6 August, 1752. The details that follow are derived from the
same journal for 4 August, 1752, where they are related of “one of
the public gardens on the other side of the water.” Possibly
Vauxhall is intended, but if not literally true of Cuper’s Gardens,
they seem sufficiently applicable to them.
[282] Boswell, Life of Johnson, ed. Croker, chap. xli. p. 366.
[283] Nollekens, ii. 201.
[284] The Folly was occasionally moored off the Bank side
(Wheatley, London Past and Present, “The Folly”).
[285] Amusements Serious and Comical, part ii. “The Thames.”
[286] Pepys (Diary, 13 April, 1668) jots down in his daily
expenditure a shilling spent “in the Folly.” From the circumstance
that he makes no special comment on the place it may perhaps
be inferred that he was already acquainted with it from previous
visits.
[287] Tom D’Urfey, A Touch of the Times, 1719.
[288] Walford, iii. 290, 291.
[289] Walford’s statement (Old and New London, vi. 388) that
they adjoined Cuper’s Gardens is not quite accurate. Four strips
of land belonging to four different proprietors are marked in the
map in Strype’s Stow (1720) as lying between the Belvedere
Gardens and Cuper’s Gardens.
[290] The proprietor, William Hagley, issued a halfpenny token
“at ye Restoration in St. George’s Feilds.” Boyne’s Trade Tokens
of the Seventeenth Century, ed. Williamson, p. 1036, No. 357.
[291] Advertisement in the Country Journal or the Craftsman,
31 March, 1733, where the celebrated “Purging Spring” and the
Chalybeate Spring “lately discovered” are mentioned, “at Mr.
Lewis’s, commonly called the Restauration Gardens in St.
George’s Fields.”
[292] The water was also to be obtained at a corkcutter’s under
Exeter Change in the Strand.
[293] Loudon’s Arboretum et frut. Brit. vol. i. p. 75. Nichols,
Parish of Lambeth, p. 84, says “about the year 1777.”
[294] Notes and Queries, 7th series, xi. p. 87 (communication
from Lieut.-Col. Capel Coape).
[295] This appears from the evidence brought forward in the
prosecution of Grist; see The Whitehall Evening Post for May 7 to
May 10, 1796 (referring to May 7).
[296] Newspapers cited by E. M. Borrajo in Notes and Queries,
7th ser. xi. 138.
[297] “The English translator of Lamotte’s Life says she fell
from the leads of her house, nigh the Temple of Flora,
endeavouring to escape seizure for debt, and was taken up so
much hurt that she died in consequence. Another report runs that
she was flung out of window.... Where the Temple of Flora was, or
is, one knows not” (Carlyle, Diamond Necklace, note near end).
The Temple of Flora alluded to was certainly in London, and there
can be no reasonable doubt that the popular resort now described
is the place in question.
[298] At the period when the gardens were open “The Asylum”
(i.e. Female Orphan Asylum) stood where Christ Church now
stands.
[299] Cp. Wilkinson, Londina Illust. vol. ii. “Pantheon Theatre.”
[300] Allen (History of Lambeth, 319) states that the Apollo
Gardens were suppressed about 1791, but this is certainly
erroneous, as the gardens were frequently advertised in 1792.
Kearsley’s Strangers’ Guide to London (1793?) mentions the
place as “the resort of company in the evenings,” and says that
music was occasionally performed there. The Temple of Apollo
was described about 1796–7 in A Modern Sabbath as already
becoming ruinous, and it is there stated that Claggett, the
proprietor, had become bankrupt. A newspaper paragraph of
December 1796 refers to a field opposite the Asylum, close by
“the ditch that encircles that place of late infamous resort, the
Apollo Gardens.”
[301] This was probably the orchestra that seems to have
stood in the centre of the gardens and not that in the concert
room.
[302] Cp. a token of 1651 (“At the Dogg and Ducke in
Southwarke,” type, Spaniel with Duck in mouth) in Boyne’s Trade
Tokens, ed. Williamson, p. 1022, there assigned to The Dog and
Duck in Deadman’s Place, Southwark, by Mr. Philip Norman, who,
however, suggests the possibility of its belonging to the Dog and
Duck in St. George’s Fields. A specimen is in the British Museum.
[303] The ponds are marked in Rocque’s Map, circ. 1745. The
duck-hunting probably took place at an early period, not later than
circ. 1750.
[304] Newspaper cutting of 1731 (W. Coll.): see also The
Country Journal or the Craftsman for 12 Aug. 1732; also 26 Aug.
1732.
[305] Johnson to Mrs. Thrale, 10 July, 1771, Letter viii. in
Johnson’s Works (ed. Murphy), xii. 338.
[306] A specimen in British Museum (from Miss Banks’s Coll.).
Silver, size 1·25 inch; Obverse: Lazarius Riverius.—Non omnibus
dormio.—Miseris succurrere disco. Bearded head of Rivière, to
left; beneath head, the number “18” incised. Reverse: The original
Spaw in St. George’s Fields so memorable in the Plague, 1665.—
For the proprieters (sic) T. Townshend Alchemist to his Majesty,
1760. Another specimen described in C. A. Rudolph’s Numismata
(relating to medical men), 1862, p. 45, has the words “Robert
Baker, Esq., Twickenham,” evidently the subscriber’s name,
engraved on the edge.
[307] The water continued to be advertised in newspapers of
1771–1779. Hedger afterwards put in his nephew Mills (or Miles)
to conduct the house which is said to have yielded Hedger £1,000
a year, but evidently himself remained the moving spirit.
[308] On the “Maid of the Oaks,” see Baker’s Biog. Dram.
[309] The Dog and Duck may have been more respectably
conducted for a time. On 28 May, 1792, a charity dinner of the
Parish of St. Thomas, Southwark, was held there (engraved
invitation ticket in W. Coll.).
[310] The Dog and Duck and the Apollo Gardens were for a
time within the Rules of the King’s Bench Debtors’ Prison (De
Castro’s Memoirs, pp. 126, 134).
[311] In De Castro’s Memoirs (1824) it is stated that he died
“about two years ago,” which indicates the year 1822, or possibly
the year 1810 (for part of the Memoirs were apparently written
circ. 1812) as the date of his death. He was certainly alive,
however, during part of the year 1810.
[312] Lambeth Wells are marked in the map of 1755 in Stow’s
Survey.
[313] They were of smaller extent than the Cumberland
Gardens, their river-side neighbour situated a little further south.
[314] One account calls him Nathan Hart.
[315] “Riley’s Gardens, Vauxhall,” mentioned in Trusler’s
London Adviser, 1786, are doubtless identical with Reilly’s
Cumberland Gardens.
[316] In the Picture of London for 1829 the Cumberland
Gardens are named in the list of places of London amusement,
but it is probable that this entry has been inadvertently copied
from a previous edition (1823) of the work. Cp. Allen, Lambeth
(1827), p. 379.
[317] Timbs (Curiosities of London, 1868, p. 18) says that
Price’s Candle Manufactory occupied the site, but in the Post
Office Directory map of 1858 the “Phœnix Gas Works” are
marked immediately south of Vauxhall Bridge and the Candle
Works still further south, i.e., beyond the Vauxhall Creek which
formed the southern boundary of the gardens.
[318] In the advertisements the name Vauxhall Gardens first
appears in 1786, but many years before that date the place was
often popularly known as Vauxhall Gardens.
[319] The place was at first generally called The New Spring
Garden. Cunningham (Handbook of London, s.v. “Vauxhall
Gardens”) and other modern writers suppose that it was called
New to distinguish it from the old Spring Garden at Charing
Cross, and this view seems to receive some countenance from a
passage in Evelyn’s Fumifugium, 1661, quoted by Cunningham. It
must be borne in mind, however, that there existed at Vauxhall
shortly after the Restoration, two Spring Gardens which seem to
have been distinguished as the Old and New. This appears very
distinctly from the following passage in Pepys, under date 29 May,
1662:—“Thence home and with my wife and the two maids and
the boy took the boat, and to Foxhall, where I had not been a
great while. To the Old Spring Garden, and there walked long,
and the wenches gathered pinks. Here we staid, and seeing that
we could not have anything to eate but very dear, and with long
stay, we went forth again without any notice taken of us, and so
we might have done if we had had anything. Thence to the new
one, where I never was before, which much exceeds the other;
and here we also walked, and the boy crept through the hedge
and gathered abundance of roses, and after a long walk, passed
out of doors as we did in the other place.”
Somewhat earlier (2 July, 1661), Evelyn in his Diary has the
entry “I went to see the New Spring Garden at Lambeth, a pretty
contrived plantation.” This probably, if not quite certainly (for

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Multidisciplinary Approach to

Osteoporosis From Assessment to

Sarcoma A Multidisciplinary Approach to Treatment

Sarcoma A Multidisciplinary Approach to Treatment 1st

Perfectionism A Relational Approach to

From Human Attention to Computational Attention A

Megaproject Management A Multidisciplinary Approach to

Clinical Guide to Assessment and Treatment of

Dysphagia Assessment and Treatment Planning A Team

Pain Management for Clinicians A Guide to Assessment

ISBN 978-3-319-75108-5 ISBN 978-3-319-75110-8 (eBook)

Library of Congress Control Number: 2018949650

© Springer International Publishing AG, part of Springer Nature 2018

I ntroduction to Interdisciplinary Approach to Osteoporosis:

Rome, Italy Andrea Lenzi

1 Anatomy and Physiology of Skeletal Tissue: The Bone Cells�������������������� 1

Part I Endocrinologicic and Metabolic Regulation

10 Bone and Diabetes�������������������������������������������������������������������������������������� 153

Part II Prevention and Treatment

© Springer International Publishing AG, part of Springer Nature 2018 1

cortical bone is mainly composed of cylindrical units known as osteons or Haversian

1.2 The Functions of the Bone

The bone is currently considered a multifunctional tissue. Indeed, it plays roles in

Furthermore, human osteoclast-poor osteopetrosis has been associated to inacti-

transcriptionally active chromatin) whereas mitigates H3K27me3 (a mark of silent

OSCAR, FcRγ, and DAP12

Tumor Necrosis Factor-α (TNF-α)

Another molecule that negatively affect TNF-α pro- osteoclastogenic effect is

a synergic on osteoclastogenesis. However, in conditions in which RANKL is severely

IL-17 has been demonstrated to be implicated in osteoclastogenesis augmenta-

1.6 Transcription Factors Affecting Osteoblastogenesis

Runt domain-containing transcription factor (Runx2) represents a master switch for

Activating Transcription Factor 4 (ATF4)

Activating Protein 1 (AP1)

1.7 Molecules Affecting Osteoblastogenesis

deletion of β-catenin in embryonic mesenchymal progenitors abolishes mature

OCs express semaphorin 4D (Sema4D), which strongly suppresses bone forma-

The Myokine Irisin

1.9.1 Development and Maintenance of the Osteocytic Network

The differentiation from OBs to osteocytes is mediated by several proteins control-

Dentin Matrix Acidic Phosphoprotein-1 (DMP-1)

1.9.2 Phosphate Metabolism and Matrix Mineralization

showed hyperphosphatemia, decreased BMD, reduced bone formation, and accu-

1.9.3 Regulation of Bone Formation and Resorption

Osteocalcin (OCN), the most abundant non-collagenous protein present in the

marker of OBs. However, in mice OCN is expressed at higher levels in osteocytes

24. Yasui T, Hirose J, Tsutsumi S, et al. Epigenetic regulation of osteoclast differentiation:

100. Gómez-Orte E, Sáenz-Narciso B, Moreno S, et al. Multiple functions of the noncanonical

And there they sit so pleasant and cool,

(Lines in Hone, loc. cit.). There is now a public house called

“For Cupid’s Bowers she hires the willing scull ...

[278] The Complete Letter-writer, Edinburgh, 1773, quoted in

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I ntroduction to Interdisciplinary Approach to Osteoporosis:

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1 Anatomy and Physiology of Skeletal Tissue: The Bone Cells�� 1

Part I Endocrinologicic and Metabolic Regulation

10 Bone and Diabetes�� 153

Part II Prevention and Treatment

1.2 The Functions of the Bone

1.6 Transcription Factors Affecting Osteoblastogenesis

1.7 Molecules Affecting Osteoblastogenesis

1.9.1 Development and Maintenance of the Osteocytic Network

1.9.2 Phosphate Metabolism and Matrix Mineralization

1.9.3 Regulation of Bone Formation and Resorption