METABOLIC AND

ENDOCRINE
DISORDERS

Taken from: Apley’s SYSTEM OF

ORTHOPAEDICS AND FRACTURES
by dr. M Mulky Yasin
 BONE COMPOSITION
 The Matrix
 Bone mineral : mainly Ca & P

 Bone cells : eosteoblast, osteocyte,

osteoclast
 BONE STRUCTURE
 Immature bone → woven
bone
 Mature tissue → lamellar
bone
– Compact (cortical bone) →
esp. the shaft of tubular
bones, subchondral plate →
haversian system or osteon
– Cancellous (trabecular
bone) → interior meshwork
of all bones → the end of
tubular bones & vertebral
bodies
– Haversian system
 BONE MODELLING AND REMODELLING
Endochondral ossif
→ proliferating cartilage : epyphyseal growth plate
BONE GROWTH
Membranous ossif
→ ossif in connective tissue : subperiosteal new bone

 Modelling : osteoclastic resorption ↔ osteoblastic formation of bone

 Remodelling : continuous replacement old bone by new bone
 HISTOLOGY

BONE REMODELLING
 REGULATION OF BONE TURN
OVER AND MINERAL EXCHANGE
 >98% Ca & 85% P in bone
 Control Ca >> critical than P
 CALCIUM
– Essential : nerve conduction, muscle contraction
– Recommended daily intake : 800-1000mg (20—
25mmol)
– Abs : mediated by vit D & requires Ca:P ratio
– Abs ↓ by >> intake P, oxalates, phytates, fats,
certain drugs and malabsorption
– Compensatory system regulated by paratiroid
hormon & vit D metabolite
 Effect of a fall in calcium serum

Serum Ca falls

Increase secretion of PTH

Increase tubular Increased Increased

reabsorption of Ca 1,25-DHCC osteoclastic activity

Increased intestinal Bone resorption

absorption of Ca
Release of Ca from bone

Serum Ca rises
 PHOSPHOR

– >>> in diet
– Abs : small intestine
– Abs ↓ by antacid
– Regulated by PTH & phosphatonin
 MAGNESIUM

– f/ efficient secretion & peripheral action

of PTH
 VITAMIN D
– Cholecalciferol (active metabolite) → transport
& abs Ca, bone remodelling
– 400iu/day
– + PTH → osteoclast resorption in bone
– Assist osteoid mineralisation
 PARATHYROID HORMONE
– Renal tubular → ↑ excretion P
– Bone
 ↑ osteoclastic resorption by stimulate osteoblast to
prepare bone surface for resorption & initiate
osteoclast chemotaxis
 ↑ release Ca & P into blood

 Stimulation ostecytic osteolysis

– Intestine → ↑ Ca absorption by promoting vit D

conversion
 CALCITONIN
– Secreted by C cells of thyroid
– Suppresses osteoclastic bone resorption & ↑
renal Ca excretion
 OTHER HORMONES
– OESTROGEN
 Stimulate Ca absorption
 Protect bone from unrestrained action of PTH
 Withdrawal → bone depletion & frank osteoporosis
→ menopause
→ amenorrhoeic young women

– ADRENAL CORTICOSTEROIDS
osteoporosis ↑ bone resorption
↓ ↓ bone formation
∑ >>> ↓ intestinal Ca abs
↑ Ca excretion
↓ collagen synthesis

– THYROXIN
↑ Formation & resorption
 Hyperthyroidism → high bone turn over & osteoporosis
 LOCAL FACTORS → important mediators of
intimate proceses
– Insulin like growth factor I (somatomedin C)
→osteoblast proliferation & activity
– Transforming growth factors
→ osteoblastic activity
→ coupling of resorption & formation
– Interleukin 1 (IL-1) & Osteoclast activating factor (OAF)
→ powerful activators of bone resorption
→ osteoporosis in inflammatory disorders, multiple
myeloma,
other malignant tumours
– Prostagalandins
→ regulate osteoclastic & osteoblastic activit
→ ↑ bone resorption in inflammatory disorders
→ bone destruction & hypercalcemia in metastatic bone
disorders
– Bone morphogenetic protein
→ ↑ chondrogenesis & bone formation
 MECHANICAL STRESS
→ WOLFF’S LAW
Architecture & mass of
the skeleton are
adjusted to withstand
the prevailing forces
imposed by functional
or deformity
Compression → more
bone formation
Tension → bone will thin
down
 ELECTRICAL STIMULATION
induced electrical potentials can affect
bone formation & resorption
 OTHER ENVIRONMENTAL FACTORS

– moderate rises in temperature or

oxygen tension → ↑ bone formation
Chronic acidosis → ↑ bone resorption
Chronic alkalosis → ↓ bone resorption
– Dietary phosphate/pyrophosphate → ↓
bone resorption
– Fluoride → ↑ oteoblastic activity
 AGE RELATED CHANGES IN
BONE
 Childhood
– Gets longer & wider
– Bone tissue quite light & porous
 Between puberty & 30 years of age
– Heavier & stronger
– Bone mass increase 3%/year
– Peak bone mass
 > 30 years
– 0,5%/year (bone loss)
 Menopause →10yrs
- bone loss in women 3%/yr
- bone depletion in black << white
 65 – 75 yrs
- bone loss 0,5 %/yr
 Men 15 or 20 years later than women
BONE GROWTH
BONE MASS & BONE STRENGTH
 Degree of mineralization varies very little
age to age or person to another

 Bone loss accompanied by

disproportionate loss of bone strength :
– Absolute diminution in bone mass
– Post menopausal bone resorption → not
all defects are repaired
– Old age → ↓ bone cell activity
 METABOLIC
DISORDERS

 Osteoporosis → quantity of bone is low

 Osteomalacia → osseous connective
tissue is present, inadequate mineralize
 Osteitis fibrosa → PTH over production
MEASUREMENT OF BONE MASS
 BMD (Bone Mineral Density)
Principle → mass and mineral content
of bone attenuate the beam of
energy
The result is compared with the
value in general population by sex
and age
 Radiographic absorptiometry
 Single energy x-ray absorptiometry
 Quantitative computed tomography
 Dual energy x-ray absorptiometry →
the method of choice
 Indications bone densitometry
– Assess the degree & progress of bone
loss
– Screening procedure for perimenopausal
women
– Monitor the effect of treatment
 Biochemical Tests
– Serum Ca & P
– Serum alkaline phosphatase → ↑ in osteomalacia
– Osteocalcin (G1a protein) → more specific marker of
bone formation
– Parathyroid hormon activity → from serum assays of
COOH terminal fragment
– Vitamin D activity → by 25-HCC concentration
– Urinary Ca & P → malabsorption, hiperPTH
– Urinary hydroxyproline excretion → for bone resorption
– Excretion of bone pyridinium compounds & telopeptides
→ much more sensitive for bone resorption
 Bone biopsy
The measure formation, resorption & remodelling of bone
 OSTEOPOROSIS
 State in which bone is fully mineralized but
its structure is abnormally porous & its
strength is less than normal
 Classified :

I regional osteoporosis i.e disuse

general osteoporosis
II primary osteoporosis →no specif causes
secondary osteoporosis → due to
endocrine, metab, neoplasma
 PRIMARY OSTEOPOROSIS
 TYPE I → high turn over → early post
menopausal syndrome
 TYPE II → low turn over → very
elderly people
 TYPE I
 ♀ at menopause → loss bone 3%/year,
before: 0,3%/year
 Risk factors
– Caucasoid (white) or Asiatic
– Family history
– History of anorexia nervosa & amenorrhea
– Low peak bone mass in early adult hood
– Early onset of menopause
– Early histerectomy
– Skinny or emaciated build
– Dietary insufficiency
– Alcohol abuse
– Cigarette smoking
– Chronic lack of exercise
 Clinical features
– Back pain
– Diminished height
– X-ray : wedging/compression vertebral
bodies
– Low energy fracture distal radius
– DEXA → reduced bone density
 Prevention & Treatment
– ♀ approaching menopause
 Maintainadequate levels of dietary Ca & vit D
 Keep up high level of physical activity

 Avoid smoking, alcohol

– Oestrogen medication
(HRT)
 The most effective way of
maintaining bone density
& reduce fracture
 Risk of breast & uterine Ca

 Selective use
– Bisphosphonates
 Prevent bone loss & reduce the risk of
fracture
 Side effect : GI

– Calcitonin
 Moderately good effect
– Fluoride
 Directly stimulate osteoblastic activity
 TYPE II
 Men steady loss of bone → 0,5% / year
 ♀ white → ≥ 70 years → ⅓ will have ≥ 1
vertebral fracture
 Risk factors

– ~ Type I
 Clinical features
– Exaggeration of type I
Fracture of ribs or pubic rami
classic event → femoral neck fr
– X-ray → obvious loss of trabecular marking
old vertebral compression fractures
 Treatment

– Manage the fracture → >> int fixation

– Other factors → dietary, sunlight,
exercise
– Bisphosphonates or HRT → if bone mass
markedly reduced
 SECONDARY OSTEOPOROSIS
 Most important causes
– hypercortisonism.
– Gonadal hormone deficiency
– Hyperthyroidism
– Multiple myeloma
– Chronic alcoholism
– Immobilization
 Those under 50 years should be fully
investigated
 Hypercortisonism

– In endogenous
Cushing’s
– Prolonged treatment
with corticosteroid
suppression
osteoblast
↓Ca abs
↑Ca excretion
Stimulation of PTH
 Gonadal Hormone Defficiency
– Young ♀ oophorectomy
ovarian agenesis & primary
amenorrhoea (Turner’s syndrom)
→ lack of estrogen → tx with HRT
– Decline testicular function → ↑ bone loss
→ tx with testosterone
 Hyperthyroidism
– Osteoporosis >> in hyperthyroidism
– Fractures → only in cumulative of
menopause & hyperthyroid
– Tx : both osteoporosis & hyperthyroid
 Multiple Myeloma & carcinomatosis
– Bone loss ~ overproduction of local osteoclast
activating factors
 Alcohol abuse
– Bone changes ~ ↓ Ca abs
liver failure
toxic effect on osteoblast func.
mild glucocorticoid effect
 Immobilization
– Regional osteoporosis → common in
immobilization limb
Nutritional Malignant disease
Scurvy Carcinomatosis
Malnutrition Multiple myeloma
Malabsorption Leukaemia

Endocrine disorders Non-malignant disease

Hyperparathyroidism Rheumatoid arthritis
Gonadal insufficiency Ankylosing spondylitis
Cushing’s disease Tuberculosis
Thyrotoxicosis Chronic renal disease

Drug-induced Idiopathic
Corticosteroid Juvenile osteoporosis
Alcohol Postclimacteric osteoporosis
Heparin

Some causes of osteoporosis

 RICKETS AND
OSTEOMALACIA

→ inadequate mineralization of bone

 Bone tissue throughout the skeleton
is incompletely calcified →
osteomalacia
 In children effect on physeal growth
& ossification → deformities of the
endochondral skeleton (rickets)
 Clinical features
– Infant
 tetany/convulsions, failure to thrive,
listlessness, muscular flaccidity
 Early bone changes → craniotabes, thickening
knees, ankles, wrists from physeal overgrowth
 Rickety rosary → enlargement costochondral
junction
 Harrison’s sulcus → lateral indentation of chest
 Distal tibial bowing
 Children who are already walking → bow legs,
knock knees, swollen joints & disturbed gait
 Severe ricket’s → coxa vara, spinal curvature,
long bone fractures
– Adults
Much more insidious
 Bone pain, backache, muscle weakness
 Vertebral collapse

 Mild kyphosis, knock knees

 Unexplained pain in the hip → stress

fracture
 X-rays
– Active ricket’s
 Thickening& widening growth plate
 Cupping metaphysis
 Bowing diaphysis

– Osteomalacia
 Looser zone (a thin transverse band of
rarefaction in an otherwise normal-looking
bone) esp. in shaft long bones, axillary edge
scapula ~ incomplete stress fractures →
calcium lacking callus
 Biconcave vertebrae ( codfish)
 Trefoil pelvis (lateral indentation acetabula)
 Spontaneous fracture : ribs, pubic rami,
femoral neck
RICKETS OSTEOMALACIA
Osteomalacia Osteoporosis

Common in ageing women

Prone to pathological fracture
Decreased bone density

Unwell Well
Generalized chronic ache Pain only after
fracture
Muscle weak Muscles normal
Looser’s zone No looser’s zone
Alkaline phosphatase Normal
increased
Serum phosphorus decreased Normal
Ca x P < 2,4mmol/l Ca x P > 2,4mmol/l
 CHARACTERISTICS OF DIFFERENT TYPES OF RICKETS
Vitamin D Renal renal
defficiency tubular glomerular
Family history - + -
Myopathy + - +
Growth defect ± ++ ++
Serum :
Ca ↓ N ↓
P ↓ ↓ ↑
Alk phos ↑ ↑ ↑
Urine
Ca ↓ ↓ ↓
P ↓ ↑ ↓
Osteitis ± + ++
fibrosa
Other Dietary Aminoacid Renal failure
defficiency or uria Anaemia
malabsorption
RENAL TUBULAR RICKETS – FAMILIAL HYPOPHOSPHATAEMIA
 HYPERPARATHYROIDISM
 Primary → adenoma/hyperplasia
 Secondary → persistent hypocalcemia

 Tertiary → secondary hyperplasia leads to

autonomous overactivity
 PRIMARY HYPERPTH
 >> solitary adenoma in one of the small
glands
 ♀ 2x> ♂

 Clinical features

– Hypercalcemia : anorexia, nausea, abdominal

pain, depression, fatigue & muscle weakness
– Hypercalciuria : polyuria, kidney stones or
nephrocalcinosis
– Chondrocalcinosis : joint symptoms
– Bone disease (<10%) : general osteoporosis,
rather than classic features ; osteitis fibrosa,
bone cysts & pathological fr.
 X-rays

– Osteoporosis & cortical erosion

– Classic → subperiosteal cortical
resorption of the middle phalanx
 Biochemical

– Hypercalcemia
– Hypophosphatemia
– Serum PTH ↑
– Alk pho ↑
 Treatment

– Usually conservative, include adequate

hydration & ↓ Ca intake
– Parathyroidectomy
 marked & unremitting hypercalcemia
 Recurrent renal calculi

 Progressive nephro calcinosis

 Severe osteoporosis

→ danger post op → hungry bone syndrome →

severe hypoCa → Tx : fast acting vit D
metabolite
 SECONDARY HYPERPTH
 Response to chronic hypoCa
 Accounts for various types of rickets
& osteomalacia
 Tx : directed of the primary condition
 RENAL OSTEODYSTROPHY
 Chronic renal failure precede diffuse bone
changes
 X-ray

– widened & irregular epiphyseal plates

– Rugger Jersey (striped) appearance → lateral
spine ~ alternate band of bone hypodensity
 Tx
– Large dose vit D (up to 500.000 iu daily)
– Epiphyseolysis → internal fixation
Renal Glomerular Osteodystrophy
 SCURVY
 Vit C defficiency causes failure of collagen
synthesis & osteoid formation → osteoporosis
 X-ray
– generalized bone rarefaction → >> long bones
metaphyses
– Ring sign → dense transverse bands at the juxta
epiphyseal zones
→ & around the ossific centres of
epiphysea
 Infant → irritable & anaemic
gums may spongy & bleeding
subperiosteal hemorrhage → excruciating
pain & tenderness near joint
SCURVY
 HYPERVITAMINOSIS
 Hypervit A → in children → >>>
dose
X-ray → increased density in
metaphyseal region & subperiost
calcif.
 Hypervit D → >>> vit D given

exerts PTH like effect

 FLUOROSIS
 Fluorine 1 ppm → reduce incidence
dental caries
 Fluorine 2-4ppm → mottling teeth
 Fluorine > 10ppm → India & Africa →
chronic fluorine intox. (fluorosis)
 Clinical features
– Backache, bone pain, joint stiffness
– Worst cases : deformities spine & lower limbs
hyperostosis → vertebral canal
→ neurologic defects
 X-ray

– Osteosclerosis, osteophytosis & ossif. of

ligamentum & fascial attachment
– Can be mistaken for those Paget’s
disease, idiopathic skeletal hyperost,
renal osteodistrophy or osteoporosis
 Tx

– No specific tx
– After exposure ceases → takes years for
bone fluorine to be excreted
 PAGET’S DISEASE (OSTEITIS
DEFORMANS)
 Characterized : enlargement & thickening of
bone, abnormal internal architecture & brittle
 >> in North America, Britain, Germany, Australia
(>3% of people > 40 year)
 << in Asia, Africa & Middle east
 Tendency familial aggregation
 Causes : unknown
 Marked increased osteoclast & osteoblast actvty
 Clinical features
– ♂=♀
– Pelvis & tibia → >>
– most → asymptomatic
– The limb look bent & feels thick, the skin unduly
warm → osteitis deformans
– Cranial nerve compression → impaired vision,
facial palsy, trigeminal neuralgia, deafness
– Steal syndromes : cerebral impairment
spinal cord ischaemia
↓
spinal claudication
lower limb weakness
PAGET’S DISEASE
 X-ray
– most typical : flame shape lesion extending
along the shaft bones
 Biochemistry
– 24 hours urinary excretion of pyridinoline cross
links → good indicator of disease activity &
bone resorption → expensive
 Complications
– Fractures
– Osteoarthritis
– Nerve compression
– Bone sarcoma
– High output cardiac failure
– Hyper Ca
 PAGET’S DISEASE

PAGET’S DISEASE
COMPLICATION
 Treatment
– Most never have any symptoms & require no
tx
– Indications for specific tx
 Persistentbone pain
 Repeated fractures

 Neurological compl

 High output cardiac failure

 Hyper Ca

– Calcitonin & biphosphonates → most effective

when disease is active & bone turn over high
– Surgery → for pathogical fr → internal fix
 Beware → blood loss is likely to be excessive
 ENDOCRINE
DISORDERS
 Anterior lobe of pituitary
– Directly affect growth
– Control activities of thyroid, gonads, adrenal
cortex
 Posterior lobe of pituitary
– Has no influence on the musculoskeletal
system
 Anterior lobe
– Secrete : pituitary growth hormone
thyrotropic
gonadotropic
adenocorticotropic
 HYPOPITUITARISM
 Anterior pituitary hyposecretion
– Intrinsic disorders
 Infarct/hemorrhage pituitary
 Infection

 Intra pitt tumors

– Extrinsic disorders
 Craniopharyngioma

Posterior lobe dysfunc.: diabetes

insipidus
 HYPOPITUITARISM
 Children
– Lorain syndrome → proportionate
dwarfism
– Frohlich’s adiposogenital syndrom →
delayed skeletal maturation
 immaturity secondary sexual characteristic
 epiphyseal slipped of hip/knee

 Adults
– Panhypopituitarism : premature
osteoporosis
 Treatment

– Depend on the cause

– If tumor + → removed or ablated
 Warning → sudden reactivation of pituitary
function after removal of tumor may result
in slipping of the proximal femoral epiphysis
– Growth hormone deff → tx biosynthetic
GH (somatotropin) succesful
ENDOCRINE DISORDER
 HYPERPITUITARISM
 Oversecretion of pitt GH ~ an
acidophil adenoma >>
 Gigantism

– GH oversecretion in childhood &

adolescence → excessive growth of the
entire skeleton, hip deformity
(epiphysiolisis), mental retardation,
sexual immaturity
– Tx : removal of pituitary tumor
 Acromegaly
– GH oversecretion in adulthood →
enlargement of bones
 Without the very marked elongation as seen
in gigantism
 Characteristic facies acromegaly
 Barrel shaped chest
 Secondary osteoarthritis

– Tx
 Operations of tumor
 Mild cases : give GH suppressants

( somatostatin analogue or bromocriptine,

dopamin agonist)
 ADRENOCORTICAL
DYSFUNCTION
 Adrenal cortex secretes :
– Mineralocorticoid (aldosterone)
– Glucocorticoid ( cortisol) → has profound
effects on bone & mineral metabolism ; →
supression osteoblast activity
 ↓Ca abs
 ↑ Ca excr

 ↑ PTH activity

 ↑ Bone resorption

 ↓ formation
 Hypercortisonism (Cushing’s
syndrome)
– Glucocorticoid excess, caused by
↑ Pitt secretion of ACTH
 ↑ Secretion by adrenal cortex (usually due to
steroid secreting tumor)
 >>> tx with glucocorticoid

– Clinical feature ~ Cushing’s syndrome

 Moon face
 Trunk distinctly obese
 Abdominal striae

– X-ray : generalized osteoporosis

 Management
– Problems
 Fractures & wound heal slowly
 Bones provide little purchase for internal fixation
 Wound breakdown & infection >>>
 Patients generally less fit

– Prevention
 Systemic corticosteroid only when essential & low
dose
 If tx prolonged → Ca supplement (>1500mg/day)
+ vit D
 Post menopausal & elderly men → HRT
 Bisphosphonates → effective for bone loss &
fracture
– Treatment
 Treat the fracture & control bone pain

 THYROID DYSFUNCTION
HYPOTHYROIDISM
 Congenital hypothyroidism
(cretinism), caused by
– Developmental abnormalities thyroid
– In endemic form in areas of iodine deffic
– The child could become severely
dwarfed & mentally retarded
– X-ray : irregular epiphyseal ossification
– Tx : thyroid hormone is essential
 Juvenile hypothyroidism
– Less severe than the congenital
– Growth & sexual development retarded
– X-ray : epiphyseal fragmentation appearance
– Tx : thyroid hormone
 Adult hypothyroidism (myxoedema)
– Result from primary disorder of thyroid func &
iatrogenic suppression thyroid
– Onset slow & long period of non specific
symptoms
– Tx : thyroxine → effective & have to be
continued for life
HYPERTHYROIDISM
 ~ previous
 PREGNANCY
 Pregnant
>> muskuloskeletal
symptoms, due to
– Hormonal changes
– Increased weight & unusual posture
 Backache, caused by

– Lordotic posture → tx postural exercise

– Increase laxity of pelvic joint ~
secretion of relaxin
 X-ray : show increase sclerosis near
sacroiliac joint → osteitis condensans ilii
 Carpal tunnel syndrome
– Caused by fluid retention & soft tissue
swelling
– Operation : avoid
– Tx
 Wristsplint
 Recover after child birth

 Rheumatic disorders
– Px with rheumatoid arthritis → improve
dramatically
– Px with systemic lupus eritematosus →
could become severe exacerbation
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