Bone health: biology and nutrition.

PURPOSE OF REVIEW: Recent findings in the influence of dietary patterns, dairy products, beverages and microbiota composition and function on bone health are reviewed and discussed. RECENT FINDINGS: Evidence is accumulating on the increased risk of fracture in individuals following a vegan diet. Meta-analysis of randomized controlled trials indicates a favourable, though of low amplitude, effect of dairy products on bone mass accrual during childhood and adolescence. Though mostly based on results from observational studies, it seems that dairy product consumption, particularly fermented dairy products, is associated with a lower risk of hip fracture. Regular green tea drinkers may have a lower fracture risk than tea abstainers. Magnesium intake is beneficial for bone health. Prune supplements prevents bone loss in untreated postmenopausal women. This seems to be associated with modification of gut microbiota. SUMMARY: This information should help the medical practitioners facing questions from their patients on how to protect bone health through nutrition.

Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group.

Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.

Early serum IGF-I response to oral protein supplements in elderly women with a recent hip fracture.

BACKGROUND & AIMS: In patients with recent hip fracture, reduced serum IGF-I in relation to protein undernutrition is frequent. Elevation of circulating IGF-I in response to a daily oral supplement of 20 g of casein was observed after 6 months. This study determined if the response to casein as compared to whey protein can be observed as early as after one week. METHODS: 45 women were randomized after recent hip fracture in 3 groups receiving a preparation of 20 g of casein, an isocaloric supplement of 20 g of whey protein or an isocaloric supplement of 15 g of whey protein combined with 5 g of essential amino acids (a.a.). RESULTS: A similar significant elevation of serum IGF-I was already observed after 7 days for casein (+37.3 microg/L), whey (+29.4) and for whey+a.a. (+34.3). From day 7-28, no further significant rise in IGF-I was recorded. CONCLUSION: After one week of protein supplementation, the percent increase of IGF-I was of similar magnitude to that previously observed after 6 months of protein supplementation. It suggests that in hip fracture patients, long-term effects of various protein preparations on IGF-I could be predicted from changes observed as early as 7 days after the onset of supplementation.

Gene-environment interactions in the skeletal response to nutrition and exercise during growth.

The amount of bone mineral mass acquired at the end of growth, the so-called 'peak bone mass', is considered to be a major risk factor for the occurrence of fragility fractures during adult life. Many interrelated factors can influence the accumulation of bone mass during growth, including genetics, sex, ethnicity, nutrition (e.g. calcium, vitamin D, protein), hormonal factors (e.g. sex steroids, insulin-like growth factor I), physical activity and exposure to various risk factors (e.g. alcohol, smoking, certain medications). Family and twin studies have estimated that up to 60-80% of the variance in peak bone mass is attributable to genetic factors. It can be predicted from epidemiological studies that a 10% increase in peak bone mass would reduce the risk of fragility fractures after the menopause by 50%. Intervention studies testing the effects of increasing either calcium intake or physical activity during growth provide evidence that modifying environmental factors can positively influence peak bone mass. Nevertheless, there is large interindividual variability in the response suggesting gene-environment interactions. A few studies have reported associations between some bone-related gene polymorphisms and the osteogenic response to loading or calcium supplementation. Identifying the functionally implicated genes interacting with mechanical loading and/or specific nutrients represents a formidable but hopefully not intractable challenge.

Calcium intake and vitamin D metabolism and action, in healthy conditions and in prostate cancer.

An association between Ca intake and the risk of prostate cancer has been reported in some but not all epidemiological studies. Assuming that a pathophysiological relationship would underlie this association, a favoured hypothesis proposes that relatively high Ca consumption could promote prostate cancer by reducing the production of 1,25-dihydroxyvitamin D (1,25(OH)2D; calcitriol), the hormonal form of vitamin D. The present review analyses the plausibility of this hypothesis by considering the quantitative relationships linking Ca intake to 1,25(OH)2D production and action in healthy conditions and in prostate cancer. Changes in the plasma level of 1,25(OH)2D in response to Ca intake are of very small magnitude as compared with the variations required to influence the proliferation and differentiation of prostate cancer cells. In most studies, 1,25(OH)2D plasma level was not found to be reduced in patients with prostate cancer. The possibility that the level of 1,25(OH)2D in prostate cells is decreased with a high-Ca diet has not been documented. Furthermore, a recent randomised placebo-controlled trial did not indicate that Ca supplementation increases the relative risk of prostate cancer in men. In conclusion, the existence of a pathophysiological link between relatively high Ca intake and consequent low production and circulation level of 1,25(OH)2D that might promote the development of prostate cancer in men remains so far an hypothesis, the plausibility of which is not supported by the analysis of available clinical data.

Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche.

Both late menarcheal age and low calcium intake (Ca intake) during growth are risk factors for osteoporosis, probably by impairing peak bone mass. We investigated whether lasting gain in areal bone mineral density (aBMD) in response to increased Ca intake varies according to menarcheal age and, conversely, whether Ca intake could influence menarcheal age. In an initial study, 144 prepubertal girls were randomized in a double-blind controlled trial to receive either a Ca supplement (Ca-suppl.) of 850 mg/d or placebo from age 7.9-8.9 yr. Mean aBMD gain determined by dual energy x-ray absorptiometry at six sites (radius metaphysis, radius diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4) was significantly (P = 0.004) greater in the Ca-suppl. than in the placebo group (27 vs. 21 mg/cm(2)). In 122 girls followed up, menarcheal age was recorded, and aBMD was determined at 16.4 yr of age. Menarcheal age was lower in the Ca-suppl. than in the placebo group (P = 0.048). Menarcheal age and Ca intake were negatively correlated (r = -0.35; P < 0.001), as were aBMD gains from age 7.9-16.4 yr and menarcheal age at all skeletal sites (range: r = -0.41 to r = -0.22; P < 0.001 to P = 0.016). The positive effect of Ca-suppl. on the mean aBMD gain from baseline remained significantly greater in girls below, but not in those above, the median of menarcheal age (13.0 yr). Early menarcheal age (12.1 +/- 0.5 yr): placebo, 286 +/- 36 mg/cm(2); Ca-suppl., 317 +/- 46 (P = 0.009); late menarcheal age (13.9 +/- 0.5 yr): placebo, 284 +/- 58; Ca-suppl., 276 +/- 50 (P > 0.05). The level of Ca intake during prepuberty may influence the timing of menarche, which, in turn, could influence long-term bone mass gain in response to Ca supplementation. Thus, both determinants of early menarcheal age and high Ca intake may positively interact on bone mineral mass accrual.