Journal of Aging Research & Clinical Practice©

NUTRITION AND OSTEOPOROSIS

V.E. Bianchi1, L.J. Dominguez2, M. Barbagallo2

Abstract: Objectices: Osteoporosis is a major global health problem resulting in an increased incidence of fractures, reduced quality
of life, and a high mortality rate. Osteoporosis is a multifactorial pathology that includes heritability, sex hormone deficiencies,
GH/IGF-1 axis dysfunction, and immobility. The aim of this review is evaluate the recent evidences regarding nutritional
interventions in osteoporosis and fracture healing. Methods: The research was conducted on the Cochrane Central Register of
Controlled Trials (CENTRAL), MEDLINE, EMBASE database. The following key words were used: Nutrition and osteoporosis,
protein and osteoporosis, lipids and osteoporosis, micronutrients and osteoporosis. Results: We matched 135 clinical studies; the
largest number have investigated the effect of isoflavones (26), than protein, calcium and vitamin D, vitamin D and K, dietary
intervention, zinc, magnesium. The most important effects on bone metabolism is related to dietary intervention and protein
intake. Uncertain results about isoflavones, vitamin D and calcium, while micronutrients such as zinc, magnesium and vitamin
K are useful. Conclusion: The reduced caloric intake and weight loss are risk factors highly related to osteoporosis and delayed
fracture healing. An high caloric and protein intake have a favorable effect on bone mass and recovery after surgery and act on
IGF-1 secretion, the major hormone regulators of bone formation. The effects of supplements such as calcium, vitamin C, vitamin
D, vitamin K, magnesium, and zinc are necessary as well.

Key words: Nutrition, osteoporosis, vitamin D, calcium, bone mass density.

Introduction protein, carbohydrates, lipids and osteoporosis,

micronutrients and osteoporosis. The filters activated
Nutritional is one of the basic factor regulating bone were: published in the last 10 years, humans and only
growth, development and accrual for all the life (1, 2). In randomized controlled trials. No study with intervention
young and aged people nutrition play an important role or conventional medicine were considered.
in regulating muscle efficiency and bone metabolism (3).
Macro and micronutrients can affect bone mass directly Results
and through the stimulation of various hormones such
as leptin (4) and IGF-1 (5). The purpose of this review is
We have matched one hundred and thirty-five clinical
to report recent evidences that evaluate the effect of the
trials evaluating the effect of isoflavones (twenty-six)
nutritional intervention (caloric intake, macronutrients,
protein (eighteen),calcium (seventeen), Vitamin D
micronutrients and dietetic supplements) on bone
plus calcium (sixteen), calcium (seventeen), vitamin
metabolism in patients with osteoporotic, e.g. hip,
D (sixteen), dietary intervention (thirteen), vitamin K
fractures. Finally, the suggestions for the best nutrition to
(eleven), herbs and fruit (seven), zinc (six), magnesium
prevent osteoporosis and fracture healing are given.
(four) on bone metabolism in postmenopausal women.
Methods
Incidence of osteoporosis and its complications
We searched on the following electronic databases last
Osteoporosis is a major global health problem
ten years to January 2014: the Cochrane Central Register
characterized by a progressive skeletal bone loss with
of Controlled Trials (CENTRAL), MEDLINE, EMBASE
deterioration of bone strength leading to fragility
the following key words: nutrition and osteoporosis,
fractures (6). Osteoporosis is estimated to affect 200
1. Clinical Center Stella Maris, Department of Nutrition and Metabolism, San million women worldwide - approximately one-tenth of
Marino; 2. Geriatric Unit, Dept. of Internal Medicine and Specialties (DIBIMIS),
University of Palermo, Italy women aged 60, one-fifth of women aged 70, two-fifths
of women aged 80 and two-thirds of women aged 90
Corresponding Author: Vittorio Emanuele Bianchi, Clinical Center Stella Maris,
Department of Nutrition and Metabolism, San Marino, email: dott.vbianchi@gmail.
(7). In the year 2000, there were an estimated 9 million
com osteoporotic fractures worldwide, of which 1.6 million
Received March 26, 2014
1
Accepted for publication April 24, 2014
JOURNAL OF AGING RESEARCH AND CLINICAL PRACTICE©
were at the hip, 1.7 million at the forearm and 1.4 million
were clinical symptomatic vertebral fractures and the
trends have been more pronounced in women than in
men (8). After hip fracture it was estimated an 12-20%
excess deaths, but due generally to underlying medical
conditions unrelated to osteoporosis. The mortality rate
in patients affected by osteoporotic fracture is of great
relevance with incidence of 12% al 24% (9). In a recent
meta-analysis was showed that patients with hip fracture
the risk for all-cause mortality during the first 3 months
is increased from 5 to almost 8 fold (10). Various factors
may contribute to the market increase in mortality risk
after postoperative hip fractures such as pulmonary
embolism (11), infectious complications (12), heart failure
(12), or cardiovascular or pulmonary complications (13).
Pathogenesis of Osteoporosis
The bone health is the expression of complex
interaction of many factors. While osteoporosis has a
high heritable component (14), great relevance have
sex steroids(15), GH/IGF-1 axis(16) ,cytokines (17, 18),
physical inactivity (18) and immobilization and smoking
(19). Although under evaluated, nutritional deficiencies
play an important role in demineralization of bone
underlying many hormonal and biological processes.
Nutrition and the GH/IGF1 axis
Growth Hormone (GH) and Insulin Growth
Factor-1 (IGF-1) have a primary importance on normal
longitudinal bone growth and plays a prominent
regulatory role in skeletal development and mineral
acquisition in adult life (16). GH is secreted by the
anterior hypophysis and act enhancing the biosynthesis
of IGF-1 in the liver and is essential for cellular growth,
differentiation, survival, and cell cycle progression
(20). IGF-1 play a critical role on bone growth, bone
development and bone mass accrual (21). A reduction
of IGF-1 level in human is associated to an increased
risk of all fractures in men (22) and in women (23).
Nutrition is a basic system regulating the human
development and disrupts the GH-IGF-1 axis causing
a reduction of circulating IGF-1 level (24) and affect
greatly the IGF-1 secretion (25). In conditions of increased
nutrition, GH first induces a greater increase in serum
IGF-1 concentration(26), in dietary restriction (fasting),
a marked decline of circulating IGF-1 level has been
observed (25).
Dietary intervention
A special nutritional supplement delivered to elderly
subjects with osteoporosis improved serum vitamin
D and reduced serum PTH and osteocalcin levels but
did not affect BMD (27, 28), while in others studies a
2
significant relationship between nutrients and BMD have
been shown(29, 30) . Dietary improvement have some
favorable changes in IGF-I and PTH levels compared
to calcium supplementation alone (31) and in elderly
women with low BMI is associated with a reduction
in bone resorption with a small positive effect on bone
formation (32). The nutrition supplement resulted in
lower complication rates and mortality at 120 days
postoperatively (2, 33) , but lack of clinical improvements
was observed in non-malnourished hip fracture patients
(34). Bass et al. (35) hypothesized that as long as nutrition
is sufficient to allow anabolic conditions and replete
hormone levels, the effect of exercise on bone strength
will be proportional.
Protein intake
Dietary protein have an opposing anabolic and
catabolic bone effects: protein is a major constituent
of bone, but acidic amino acids may promote bone
resorption; however, higher protein intake does not have
an adverse effect on bone in premenopausal women
(36). Low protein intake is detrimental for bone health
and recent epidemiologic studies demonstrated an
increased rates of bone loss in individuals habitually
consuming low-protein diets and that high-protein
diets are not detrimental to bone (37). Under-nutrition
with a reduced protein intake is an important risk factor
for hip fracture. In the NHANES I Study, hip fracture
was higher in patients with poor nutritional status,
evident in inadequate dietary intake, (38) as low BMI
(39). Protein-energy under-nutrition present at hospital
discharge appears to be a strong independent risk factor
for mortality during the subsequent 4-5 years or longer
(40). An high protein intake have a positive effect on bone
mineral density and on a reduced risk of hip fracture (35).
Various clinical studies have evidenced that high intake
of dietary protein, especially from animal sources, may
be associated with a reduced incidence of hip fractures
in postmenopausal women (32, 41-46) and a dose
dependent effect of protein intake on bone formation
was also observed (32, 47). Long-term effects of high
dietary protein intake on muscle and bone structure in
the elderly shows that high protein intake is associated
with long-term beneficial effects on muscle mass and
size and bone mass (45). Misra et al. (42) examined
the association between energy-adjusted protein intake
and hip fracture risk in elders and found that increased
protein intake was associated with a decreased risk
of hip fracture compared to those in the lowest and
the minimum protein intake suggested is 70 gr/day.
Vatanparast et al. (48) indicate that protein intake has a
beneficial effect on the bone mass of young adult females
when calcium intake is adequate. Protein, in the absence
of sufficient calcium, does not confer as much benefit to
bone. Conversely, other studies showed a negative effect
of high protein diet on bone mass accrual (44, 49).

Isoflavonoids
Isoflavonones are a plant-derived estrogen-like
compounds without effects on uterotrophic (50) . This
dietary supplement has been used in postmenopausal
women to counteract the effects of low estrogen level
and bone loss from many years but the effects are still
controversial. We matched twenty seven studies clinical
studies and in the majority the supplementation with
isoflavones in postmenopausal women did not show
any estrogenic effects on bone turnover markers and
were unable to prevent lumbar and whole body bone
loss (51-60) , while other studies evidenced a significant
favorable effect on bone and calcium homeostasis (61-
64), and others showed a modest ability to suppress
bone resorption (54, 65-68). Also with moderate-intensity
endurance exercise training associated no impact on
BMD and no additive effects of exercise on BMD has
been observe (57). In the studies reported there was
a great variable in methodology, such as healthy
postmenopausal women or with severe osteoporosis,
number of patients involved, different dosage and
duration of isoflavones administration and this
can explain the different results reported. A recent
systematic meta-analysis revealed that soy isoflavones
supplements significantly increased BMD and decrease
the bone resorption marker but the effect is relative to
menopausal status, supplement type, isoflavones dose
and intervention duration(69). Another meta-analysis
evidenced that the ingestion of 84 mg of isoflavones
compared with control group evidenced no significant
effects on femoral neck, hip total, and trochanter BMD
in menopausal women (70). The effects of isoflavones on
bone metabolism remain uncertain and most studies have
been done with more specific methodology considering
the degree of osteoporosis, nutritional status and total
energy intake, plasma level of IGF-1, the most important
hormone involved in bone metabolism.
Vitamin D
Vitamin D deficiency is a risk factor for bone health
and skeletal muscle that causes falls and fractures in
postmenopausal women (71). The appropriate serum
25(OH)D threshold to define vitamin D insufficiency is
50 nmol/l and with supplementation should increase
this level within the 50–75 nmol/l range. This level can
be achieved with a dose of 800 IU/day vitamin D (72),
but a supplementation with higher vitamin D dosages
(2,000-3,000 until 6.500 IU/day ) is required to achieve
a normalization of PTH (73, 74). An optimal vitamin D
repletion seems to be necessary to maximize the anti-
resorption effect on BMD changes and anti-fracture
efficacy (75). Very few studies have investigated the
efficacy of vitamin D on BMD and are still controversy.
Vitamin D supplementation does not appear to
3
NUTRITION AND OSTEOPOROSIS
influence bone loss in black women (76) and high-dose
of intermittent vitamin D regimen do not support an
effective strategy to reduce falls and fractures (77). The
administration of large doses of vitamin D is associated
with an acute significant increase in bone resorption
markers, which may explain the negative clinical results
obtained by using intermittent high doses of vitamin
D to treat or prevent vitamin D deficiency (78). There
are ongoing trials in older adults to better define the
range of doses of vitamin D supplementation associated
with specific outcomes BMD, plasma 25OHD, PTH and
biochemical markers of bone turnover (79). Vitamin D
intake above current dietary reference was not reported
to be associated with an increased risk (80). However,
intoxication can occurs secondarily from accidental
excessive uptake of vitamin D (81).
Effect of supplementation of Vitamin D plus
calcium on bone metabolism
Calcium (Ca) and vitamin D supplementation is
institutionalized elderly individuals with poor nutritional
status, can suppress secondary hyperparathyroidism,
reduce bone resorption, increase BMD and reduce
fracture risk (82). Ca and vitamin D supplements
reverse secondary hyperparathyroidism and are widely
prescribed to prevent osteoporotic fractures, with proven
antifracture efficacy when targeted to individuals
with documented insufficiencies. We matched sixteen
studies that investigated the effect of vitamin D plus Ca
administration in postmenopausal. The daily average
Ca intake in Europe has been evaluated in the SENECA
study concerning the diet of elderly people from 19 towns
of 10 European countries and in one third of subjects the
dietary Ca intake was very low, between 300 and 600
mg/day in women, and 350 and 700 mg/day in men
(83). It is well recognized the great importance of Ca
and vitamin D supplementation and it has been shown
that subject with higher Ca intake have an higher BMD
compared with those with lower Ca intake (84), and the
administration of both can decrease postmenopausal
bone loss and prevent fracture risk (85). The prevalence
of the studies reported a significant positive effect on
the skeleton, with reduction of bone resorption (86-
92), with an increased lumbar and femoral BMD (87,
89, 91, 93, 94) with an improvement of the biochemical
markers related to bone remodeling (95) and a positive
effect fractures (96), while Jakson et al. (97) found a
modest beneficial effects on hip structural features at
femoral neck. The supplementation with low-dose oral
vitamin D3 and Ca during winter may be an efficient
and inexpensive strategy for the primary prevention of
bone loss in northern latitudes (93). Interestingly, Bonjour
et al. (88) found an increased serum level of IGF-1 after
vitamin D, Ca and a fortified diet with 16 gr of protein
related to a reduction of bone loss. In most trials, the
JOURNAL OF AGING RESEARCH AND CLINICAL PRACTICE©
effects of vitamin D and Ca could not be separated and
the supplementation compared to placebo has a small
beneficial effect on BMD, and reduces the risk of fractures
and benefit may be confined to specific subgroups.
Vitamin D intake above current dietary reference intakes
was not reported to be associated with an increased risk
of adverse events (80). In one of the most important
study conducted on 36,282 healthy postmenopausal
women, Ca with vitamin D supplementation resulted in
a small but significant improvement in hip bone density,
did not significantly reduce hip fracture and increased
the risk of kidney stones (98).
Vitamins
Vitamin C. Vitamin C (ascorbic acid) is an antioxidant,
and it is well-known that ascorbic acid acts as a cofactor
for proline hydroxylase and lysine hydroxylase, enzymes
involved in the process of collagen hydroxylation (99),
stimulate procollagen, enhance collagen synthesis, and
stimulates alkaline phosphatase activity, a marker for
osteoblast formation. The effect of vitamin C on collagen
biosynthesis was confirmed by several research groups
(100, 101). Vitamin C does not increase collagen content
but induces increased collagen production within the
extracellular matrix (102). Human skin fibroblasts
exposed to ascorbic acid over time had rising levels of
type 1/type 4 collagens and type 1 procollagen synthesis
(103).
In postmenopausal women Vitamin C
supplementation at the mean daily dose was 745 mg,
administered for more than 3 years showed a BMD levels
approximately 3% higher at the midshaft radius, femoral
neck, and total hip. Women taking both estrogen and
vitamin C had significantly higher BMD levels at all sites.
Women who took vitamin C plus calcium and estrogen
had the highest BMD at the femoral neck. Vitamin
C supplement use appears to have a beneficial effect
on levels of BMD, especially among postmenopausal
women using concurrent estrogen therapy and calcium
supplements (104).
Vitamin E. The effect of the association of Vitamin
C and E is interesting. After 7 and 14 days of wound
injury, the antioxidant sol-gel vitamin C plus vitamin
E improved wound healing significantly accelerating
epidermal and dermal maturation, increasing in collagen
content, and decreasing in apoptosis formation(105).
Vitamin C plus vitamin E have a significant effect on
the proliferation and differentiation of primary
bovine osteoblasts in vitro, well evidenced by
Immunohistochemical analyses (106).
Vitamin K. high-dose of vitamin K1 (phylloquinone)
and K2 (short-chain menaquinone-4) supplementation
improved bone health after menopause. Healthy
postmenopausal women received for three years placebo
or vitamin K2 (MK-7) (180 μg MK-7/day) capsules.
decreased the age-related decline in BMC and BMD
4
at the lumbar spine and femoral neck, but not at the
total hip (107). Lamb et al.(108) demonstrated that
berberine, vitamin D₃, and vitamin K₁ produced a more
favorable bone biomarker profile indicative of healthy
bone metabolism in postmenopausal women with
metabolic syndrome. The positive effect of vitamin K2
(menaquinone-4) at the dose of with 1.5 mg/d have been
demonstrated by other authors (109-111) while vitamin
K1 has no effect on bone turnover.
Minerals
Calcium. The Ca intake is important in determining
bone health throughout the life (112) but some
conflicting results exist. A long term dietary intake of
Ca and risk of fracture of any type and osteoporosis
was investigated by longitudinal and prospective cohort
study of 61.433 women followed for 19 years. The
increases in dietary Ca intake in this female population
were not associated with further reductions in fracture
risk of osteoporosis (113). Furthermore, dietary Ca
intake and vitamin D status did not alter the effects of
zoledronate, suggesting that co-administration of Ca and
vitamin D with zoledronate may not be necessary for
bone mineralization (114). In patients with documented
osteoporosis the benefits are most apparent when a
daily dose of 1000-1200 mg Ca is complemented with
800 IU vitamin D. Compliance is the key to optimizing
clinical efficacy. While (conventionally dosed) vitamin
D has not been associated with safety concerns, recent
meta-analytic data have provided evidence to suggest
that Ca supplements (without co-administered vitamin
D) may potentially be associated with cardiovascular
risks (115), and might raise myocardial infarction risk
(116) then should be taken with caution. In a recent
double blind study conducted in postmenopausal women
was demonstrated that the Ca load decreased PTH and
CTX and raised urinary Ca. Thus, although studies
supporting the beneficial effects of Ca on bone health are
predominant in the literature, some discordance exists.
The unfavorable effect of dairy intake on the risk of
fractures is limited and most discordant studies indicate
no effect of dairy consumption on bone safety (117). Ca
is essential for bone health, although it will not prevent
bone loss due to other factors. For the elderly population,
aged 65 years and over, the RDA is 700-800 mg/day. The
optimal way to achieve an adequate intake is nutrition.
The main source of Ca in the diet are dairy products
(milk, yoghurts and cheese) fish (sardines with bones)
few vegetables and fruits and Ca supplementation may
be suggested when dietary sources are scarce or not well
tolerated.
Magnesium. Magnesium (Mg) is the second most
abundant intracellular cation in human body and about
60% of total Mg is stored in as surface of bone. Ca and
phosphate as hydroxyapatite account for 90% (118)
The Institute of Medicine recommends 310–360 mg and

400–420 mg for adult, but a subclinical Mg deficiency
due inadequate dietary Mg intake has been shown by
nutritional monitoring program (119). Mg homeostasis
is regulated through a complex network including daily
dietary intake, intestine absorption, daily fecal and
urinary output. Mg deficiency is a very rare condition but
frequently associated with chronic gastrointestinal and
renal diseases (120) and with malabsorption syndromes
such as gluten-sensitive enteropathy (121). Induced
dietary Mg deprivation in the rat at 10%, 25% and 50%
of recommended nutrient requirement was observed
bone loss, decrease in osteoblasts, and an increase in
osteoclasts by histomorphometry (122). The bone loss
in Mg deficiency subjects in humans and rat model
demonstrated low serum PTH and vitamin D levels,
which may contribute to reduced bone formation. These
data support the notion that dietary Mg intake may
perturb bone and mineral metabolism and be a risk
factor for osteoporosis. Only a few studies have his study
have demonstrated that oral Mg supplementation in
postmenopausal osteoporotic women suppresses bone
turnover (123, 124). Because Mg is a Ca antagonist,
should be considered that high concentrations of Mg
alter Ca/Mg ratio, leading to dysregulated cell functions
(125). Mg deficiency represent a concern in osteoporosis
as it is crucial for regulation of osteoblast and
osteoclast function and activity, but further clinical and
epidemiological studies are necessary to clarify whether
Mg supplementation may help to prevent bone mass loss
and osteoporosis.
Zinc. In young patients with thalassemia, zinc (Zn)
supplementation resulted in greater gains in total-body
bone mass than did placebo. Zn was well tolerated and
is worthy of investigation in larger trials in thalassemic
patients across a range of ages and disease severity (126).
Bone growth retardation is common finding in various
conditions associated with dietary Zn deficiency (127).
It has been shown that Zn has a stimulatory effect on
osteoblastic bone formation and mineralization and Zn
supplementation is a useful factor in the prevention and
therapy of osteoporosis. A recent study conducted on
728 postmenopausal women a significant relationship
between low serum Zn levels and vertebral osteoporosis
for L1-L4 spines was found (128). In that study also
the low serum levels of copper, iron and Mg appear
to be an important risk factor for osteoporosis. Other
studies evidenced that the postmenopausal osteoporotic
women may benefit from a Zn sulfate supplementation
of 220 mg/day (129-131). Zn administration significantly
increased GH, IGF-1 and IGF-BP3 (132) and increase the
effect of essential aminoacids-whey protein supplements
and decrease the serum bone resorption markers (133).
Finally, Zn is safe and well tolerated by a geriatric
population (134).
Herbs and fruit. Some evidences about the effect of
herbs on bone metabolism have been shown (135) and
that fruits and vegetables may have a bone sparing effect
5
NUTRITION AND OSTEOPOROSIS
have been shown (136) but a recent study demonstrated
that increased fruit and vegetables consumption had no
effect on bone markers in older adults (137).
Malnutrition in elderly
Nutrition influence deeply the bone metabolism at the
beginning in childhood (1) and continuing for all the life
(138) and under-nutrition is a severe not well evaluated
clinical risk. Similar to immobilization, malnutrition
have the immediate effect on bone resorption. More
specifically, protein and energy malnutrition results in
massive bone loss due to endosteal resorption in cortical
bone and trabecular thinning (139). Weight loss, a typical
condition of reduced energy food intake, often results in
bone loss and bone resorption in obese postmenopausal
women (140-142), in obese premenopausal women (143,
144) and in normal obese subjects (145). A modest weight
loss in postmenopausal women induced significant
BMD loss at hip and lumbar spine level (146) and the
perturbations in bone mass persist after partial weight
regain, independently by a regular weight-bearing
exercise continued (147). Repeated cycles of high fiber
weight loss and weight gain may increase the risk of
spinal osteoporosis (148). In a population on women
over 66 years old, a weight loss of more than 5%, during
5.5 years was followed by a 1.8 times increased risk of
hip fracture during the subsequent 4.4 years (149). A
ten years follow up data 600 the weight loss and low
body mass were associated with a 44% increased risk
of hip fracture underlining the association between
nutritional status and skeletal fragility and a loss of
total body weight and lean body mass during the first
6 months after a hip fracture has been observed (150).
Among elderly the risk of malnutrition and underweight
are persisting problems and protein-energy malnutrition
is very frequent in patients suffering of osteoporosis
or fractures (139, 151). More than 50% of elderly
patients with hip fractures are already malnourished
on admission to hospital (152) and during their hospital
stay the intake of energy food has been shown to be
considerably lower than needed (153). The sign of
catabolism continues after a hip fracture intervention ,
with significant decrease of BMD, lean body mass and
bone mass and IGF-1 reduction indicating that adequate
nutrition to preserve bone and muscle losses in elderly
patients (154). Trials with adequate nutrition reported
a significant improvement of the functional status (27)
and a reduction in bone resorption with a positive effect
on bone formation (32). Bone resorption decreased on 12
months’ liquid supplementation in community dwelling
osteoporotic individuals. A clinical study conducted by
Moschonis et al.(138) evidence a significant increase in
BMD at the trochanter, femoral neck and lumbar spine
after 30 months of fortified diet plus calcium (1200 mg/d)
and 7·5 mg/d of vitamin D3. These data are confirmed
by others (31, 155), furthermore a higher increase of
JOURNAL OF AGING RESEARCH AND CLINICAL PRACTICE©
IGF-1 was observed for the group with fortified nutrition
program compared to placebo group. The latest Cochrane
update on hip fracture aftercare conclude that multi-
nutrient feeds reduce the incidence of unfavorable
outcomes, but weak evidence exists for the effectiveness
of protein and energy feeds and clinical trial with robust
methodology are required (156).
Discussion
Muscle and bone are influenced by a nutritional
deficiency that may contribute to bone loss in aged
patients (157). The energy metabolism affects bone
mass accrual by acting on the osteoblasts that are an
important target used by insulin to control whole-body
glucose homeostasis and identify bone resorption as
the mechanism regulating osteocalcin activation (158).
The prescription of high caloric diet and high protein
diet appear to be the most important factors to increase
BMD, in decreasing the complications after hip fracture
and to improve clinical recovery after bone surgery.
Furthermore, a significant elevation of serum IGF-I was
already observed after protein supplementation (159)
Conversely, low dietary protein intake increase the risk
of complication and favor the delayed healing decreasing
plasma IGF-I and osteocalcin, reducing periosteal bone
formation. Low dietary protein induces an osteoblast
resistance to the effects of IGF-I in both cortical and
cancellous bone (160) and reduce the IGF-1 secretion
itself(25). Many clinical studies have investigated the
effects of isoflavones in postmenopausal women, but
the effects on bone metabolism remain uncertain. It
seems that isoflavones have some effect in patients with
a good energy and protein intake (61, 161). Also the
supplementation of Ca and vitamin D (Ca carbonate
mg. 1,000 with 400 units of vitamin D3) evidenced
modest and uncertain effects. The supplementation of
1000 mg/fay of Ca is not necessary because an higher
amount of Ca is content in 100 ml of cow’s milk; milk
consumption is associated with lumbar BMC and BMD
in postmenarcheal girls (162) and in postmenopausal
women (163). Furthermore, multivitamin preparations
should not be used for vitamin D treatment and
patients unnecessarily treated with vitamin D need to
be evaluated to avoid vitamin D intoxication. Between
vitamins, interestingly is the association of vitamin C
with vitamin E that have shown a significant effect on
the improving wound healing, increasing in collagen
content, proliferation and differentiation of primary
bovine osteoblasts . Vitamin C users at the mean dose
of 745 mg/day can have an higher BMD levels but this
was demonstrated only in one study (104). Vitamin K2
(menaquinone-4) have a positive effect at the dose of
with 1.5 mg/d on BMD, maintaining bone strength at
the site of the femoral neck in postmenopausal women
by improving BMC while no effect was found for
vitamin K1 (111). Between mineral supplements, Zn
6
an Mg have a significant effect on bone mineralization
and seem to be more effective than Ca. In patients
with chronic gastrointestinal and renal diseases the
Mg supplementation may help to prevent bone mass
loss and osteoporosis. Zn administration significantly
increased GH, IGF-1 and IGF-BP3 and increase the effect
of essential amino acids-whey protein supplements that
are key point on the anabolic effect on bone. Zn intake
influence (130), particularly beneficial to bone health in
postmenopausal women with low usual Zn intakes < 8.0
mg/d.
In conclusion in osteoporotic patients, increasing
daily caloric and protein intake and mineral
supplementation, particularly Zn and Mg, Vitamin C
and E have positive effects on BMD and are essential
for recovery in post-surgical orthopedic treatment.
Caution must be used for isoflavones, vitamin D and Ca.
These positive effects are more evident among elderly
malnutrition and underweight patients.
Acknowledgements: The authors thank Ms.Elisabetta Santandrea and Laura
Grossi of the Azienda USL Romagna Biblioteca medico-scientifica - Rimini for the
bibliographic support..
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