Benefits and safety of dietary protein for bone health-an expert consensus paper endorsed by the European Society for Clinical and Economical Aspects of Osteopororosis, Osteoarthritis, and Musculoskeletal Diseases and by the International Osteoporosis Foundation.

A summary of systematic reviews and meta-analyses addressing the benefits and risks of dietary protein intakes for bone health in adults suggests that dietary protein levels even above the current RDA may be beneficial in reducing bone loss and hip fracture risk, provided calcium intakes are adequate. Several systematic reviews and meta-analyses have addressed the benefits and risks of dietary protein intakes for bone health in adults. This narrative review of the literature summarizes and synthesizes recent systematic reviews and meta-analyses and highlights key messages. Adequate supplies of dietary protein are required for optimal bone growth and maintenance of healthy bone. Variation in protein intakes within the "normal" range accounts for 2-4% of BMD variance in adults. In older people with osteoporosis, higher protein intake (≥ 0.8-g/kg body weight/day, i.e., above the current RDA) is associated with higher BMD, a slower rate of bone loss, and reduced risk of hip fracture, provided that dietary calcium intakes are adequate. Intervention with dietary protein supplements attenuate age-related BMD decrease and reduce bone turnover marker levels, together with an increase in IGF-I and a decrease in PTH. There is no evidence that diet-derived acid load is deleterious for bone health. Thus, insufficient dietary protein intakes may be a more severe problem than protein excess in the elderly. Long-term, well-controlled randomized trials are required to further assess the influence of dietary protein intakes on fracture risk.

Food fortification for bone health in adulthood: a scoping review.

Food fortification can deliver essential micronutrients to large population segments without modifications in consumption pattern, suggesting that fortified foods may be formulated for populations at risk for fragility fractures. This scoping review determined the extent to which randomized controlled studies have been carried out to test the impact of fortified foods on bone outcomes, searching PubMed for all studies using the terms 'fortified AND bone', and 'fortification AND bone'. Studies were restricted to English language, published between 1996 and June 2015. From 360 articles, 24 studies met the following criteria: human study in adults ⩾18 years (excluding pregnancy or lactation); original study of a fortified food over time, with specific bone outcomes measured pre- and post intervention. Six studies involved adults <50 years; 18 involved adults ⩾50 years. Singly or in combination, 17 studies included calcium and 16 included vitamin D. There were 1 or 2 studies involving either vitamin K, magnesium, iron, zinc, B-vitamins, inulin or isoflavones. For adults <50 years, the four studies involving calcium or vitamin D showed a beneficial effect on bone remodeling. For adults ⩾50 years, n=14 provided calcium and/or vitamin D, and there was a significant bone turnover reduction. No consistent effects were reported in studies in which addition of vitamin K, folic acid or isoflavone was assessed. Results from this scoping review indicate that up to now most studies of fortification with bone health have evaluated calcium and/or vitamin D and that these nutrients show beneficial effects on bone remodeling.

Fortification of Yogurts with Vitamin D and Calcium Enhances the Inhibition of Serum Parathyroid Hormone and Bone Resorption Markers: A Double Blind Randomized Controlled Trial in Women over 60 Living in a Community Dwelling Home.

OBJECTIVE: To evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum parathyroid hormone (PTH) and bone resorption markers (BRM) as compared to iso-caloric and iso-protein dairy products in aged white women at risk of fragility fractures. DESIGN: A randomized double-blind controlled trial. SETTING: A community dwelling home. PARTICIPANTS: Forty-eight women over 60 years (mean age 73.4). INTERVENTION: Consumption during 84 days of two 125 g servings of either vitamin D and calcium-fortified yogurts (FY) at supplemental levels of 10 µg vitamin D3/d and 520 mg/d of calcium (total=800 mg/d), or non fortified control yogurts (CY) providing 280 mg/d of calcium. MEASUREMENTS: Serum changes from baseline (D0) to D28, D56 and D84 in 25OHD, PTH and in two BRM: Tartrate-resistant-acid-phosphatase-isoform-5b (TRAP5b) and carboxy-terminal-cross-linked-telopeptide of type-I-collagen (CTX). RESULTS: The 10 years risk of major and hip fractures were 13.1 and 5.0%, and 12.9 and 4.2 %, in FY and CY groups, respectively. From D0 to D84, serum 25OHD increased (mean±SE) from 34.3±2.4 to 56.3±2.4 nmol/L in FY (n=24) and from 35.0±2.5 to 41.3±3.0 nmol/L in CY (n=24), (P=0.00001). The corresponding changes in PTH were from 64.1±5.1 to 47.4±3.8 ng/L in FY and from 63.5±4.6 to 60.7±4.2 ng/L in CY (P=0.0011). After D84, TRAP5b was reduced significantly (P=0.0228) and CTX fell though not significantly (P=0.0773) in FY compared to CY. CONCLUSION: This trial in aged white women living in a community dwelling home at risk for osteoporotic fractures confirms that fortification of dairy products with vitamin D3 and calcium should provide a greater prevention of secondary hyperparathyroidism and accelerated bone resorption as compared to non-fortified equivalent foods.

Fracture history of healthy premenopausal women is associated with a reduction of cortical microstructural components at the distal radius.

OBJECTIVES: The objective of this study is to determine in healthy premenopausal women with a history of fracture which bone structural components of the distal radius are the most closely associated with a risk of fracture. METHODS AND PARTICIPANTS: The method was as follows: measurement of radial areal bone mineral density (aBMD) by DXA, microstructural components by high-resolution quantitative peripheral computerized tomography (HR-pQCT) and strength variables by micro Finite Element Analysis (µFEA) in 196 healthy premenopausal women aged 45.9 ± 3.7 (± SD) years with (FX, n = 96) and without (NO-FX, n = 100) a history of fracture. We evaluated differences in T-scores between FX and NO-FX and risk of fracture by Odds ratios (OR with 95% confidence intervals, CI) per one SD decrease, using logistic regression analysis after adjustment for age, height, weight, menarcheal age, calcium and protein intakes, and physical activity. RESULTS: In the whole group the mean radial metaphysis aBMD T-score was not significantly different from zero. In the FX as compared to the NO-FX group, the differences in T-scores were as follows: for radial metaphysis: aBMD, -0.24 (P = 0.005); for distal radius microstructure components: cortical volumetric BMD, -0.38 (P = 0.0009); cortical thickness, -0.37 (P = 0.0001); cross-sectional area (CSA), +0.24 (P=0.034); and endosteal perimeter, +0.28 (P = 0.032); and for strength estimates: stiffness, -0.15 (P = 0.030); failure load, -0.14 (P = 0.044); and apparent modulus, -0.28 (P = 0.006). T-scores of trabecular volumetric BMD and thickness did not significantly differ between the FX and the NO-FX group. Accordingly, the risk of fracture (OR, 95% CI) for 1 SD decrease in radius bone parameters was as follows: radial metaphysis aBMD: 1.70 (1.18-2.44), P = 0.004; cortical volumetric BMD: 1.86 (1.28-2.71), P = 0.001; and cortical thickness: 2.36 (1.53-3.63), P = 0.0001. The corresponding fracture risk for the strength estimates was as follows: stiffness: 1.66 (1.06-2.61), P = 0.028; failure load: 1.59 (1.02-2.47), P = 0.041; and apparent modulus: 1.76 (1.17-2.64), P = 0.006. CONCLUSIONS: In healthy premenopausal women, a history of fracture is associated with reduced T-scores in the distal radius, with the cortical components showing the greatest deficit. A reduction of one SD in cortical thickness is associated with a nearly three-fold increased risk of fracture. This finding strengthens the notion that, in healthy women, a certain degree of bone structural fragility contributes to fractures before the menopause and therefore should be taken into consideration in the individual prevention strategy of postmenopausal osteoporosis.

Impact of nutrition on muscle mass, strength, and performance in older adults.

Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid-base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0-1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate [corrected] relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B12 and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid-base balance are important elements of any strategy to preserve muscle mass and strength during aging.

Fractures in healthy females followed from childhood to early adulthood are associated with later menarcheal age and with impaired bone microstructure at peak bone mass.

BACKGROUND: Whether fractures observed in healthy children are associated with microstructural alterations and strength deficit that persists by the end of the growth period is not established. Considering the importance of pubertal timing in bone development, we also quantified the fracture risk related to later menarcheal age (MENA). PARTICIPANTS AND METHODS: We followed 124 healthy girls from mean ± sd age 7.9 ± 0.5 to 20.4 ± 0.6 yr. Fractures, MENA, and radius areal bone mineral density (aBMD) were recorded at regular intervals. At a mean age of 20.4 yr, microstructural and strength variables of the distal radius were determined by high-resolution peripheral computerized tomography and micro-finite element analysis. RESULTS: Sixty-one fractures occurred in 42 subjects. At 20.4 yr, subjects with fractures had lower aBMD at radial diaphysis (P = 0.005) and metaphysis (P = 0.008), lower distal radius trabecular volumetric density (vBMD) (P = 0.010) and thickness (P = 0.014), and reduction in stiffness (P = 0.013), failure load (P = 0.013), and apparent modulus (P = 0.046). Odds ratios revealed an increased risk of fracture for a 1-sd reduction in radial aBMD diaphysis [1.97 (P = 0.006)] and metaphysis [1.97 (P = 0.008)] and distal radius trabecular vBMD [1.89 (P = 0.011)], thickness [1.97 (P = 0.017)], stiffness [2.02 (P = 0.014)], failure load [2.00 (P = 0.014)], and apparent modulus [1.79 (P = 0.043)]. MENA occurred at a later age in subjects with fractures (P = 0.003). For MENA 1 sd (1.2 yr) later, the increase of fracture risk was 2.1 (P = 0.002). CONCLUSIONS: In healthy young women, low trabecular vBMD and thickness in the distal radius are associated with reduced bone strength and increased fracture risk during growth. This study also documents that later pubertal timing is associated with increased incidence of fracture during childhood and adolescence.

Fractures during childhood and adolescence in healthy boys: relation with bone mass, microstructure, and strength.

CONTEXT: In healthy boys, fractures result from trauma of various severity, suggesting contribution of an intrinsic biomechanical fragility. OBJECTIVES: Our objective was to characterize bone mineral mass, microstructure, and strength in boys with and without fractures. PARTICIPANTS AND DESIGN: We followed 176 healthy boys from 7.4 ± 0.5 to 15.2 ± 0.5 (mean ± sd) yr of age. OUTCOMES: Areal (a) bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry at radius metaphysis and diaphysis, total hip, femoral neck and diaphysis, and L2-L4 vertebrae. Volumetric (v) BMD and microstructure were assessed by high-resolution peripheral computerized tomography at both distal tibia and radius. Bone strength was evaluated by micro-finite element analysis. RESULTS: A total of 156 fractures were recorded in 87 of 176 boys with peak incidence between 10 and 13 yr. At 7.4 yr, subjects with fractures had lower aBMD in all sites and at 15.2 yr in femoral and spinal, but not in radius, sites. At that age, boys with fractures displayed lower trabecular (Tb) vBMD (P = 0.029) and number (P = 0.040), stiffness (P = 0.024), and failure load (P = 0.016) at distal tibia, but not distal radius. Odds ratios of fracture risk per 1 sd decrease were 1.80 (P = 0.006) for femoral neck aBMD and 1.46 (P = 0.038) for distal tibia Tb vBMD, 1.59 (P = 0.031) for Tb number, 1.53 (P = 0.072) for stiffness, and 1.60 (P = 0.056) for failure load. CONCLUSION: In a homogeneous cohort of healthy boys, fractures recorded until 15.2 ± 05 yr of age were associated with lower femoral neck aBMD and with lower distal tibia trabecular vBMD and number, stiffness and failure load. These deficits in bone mineral mass, microstructure and strength could contribute to the occurrence of fractures during growth.

Nutritional approach for inhibiting bone resorption in institutionalized elderly women with vitamin D insufficiency and high prevalence of fracture.

BACKGROUND: Nutritional approach to the deterioration of bone integrity and increased fracture risk appears to be particularly appropriate in elderly women living in nursing homes. OBJECTIVE: To investigate the beneficial effect of the consumption of soft plain cheese on bone resorption markers in institutionalized elderly women. DESIGN: Prospective, randomized crossover controlled study. SETTING: Six French nursing homes or other institutions for elderly. PARTICIPANTS: Institutionalized women ≥ 65 years old with low vitamin D status and calcium intake below 700 mg/day. INTERVENTION: Consumption of soft plain cheese made of semi-skimmed milk which was fortified by both vitamin D3 (+1.25 µg/100g) and milk extracted Ca, thus achieving a total Ca content of 151 mg/100g as compared to about 118 mg/100g for standard fresh cheese. Two servings were taken every day during the 6 weeks that preceded or followed a period of 6 weeks without soft plain cheese consumption. MEASUREMENTS: The primary end point was the change in serum carboxy terminal cross-linked telopeptide of type I collagen (CTX) selected as a marker of bone resorption. RESULTS: 29 women aged 73-94 yr were selected, 21 of them with mean age 87.2±6.1 years remained compliant. The intervention increased calcium and protein intakes by 51% (904±228 vs. 599±122 mg/d) and 33 % (74.2±17.1 vs. 55.6±12.7 g/d, mean±SD), respectively. The dietary intervention was associated with a statistically significant increase in serum levels of both 25OHD and IGF-I, while those of [corrected] CTX and TRAP5b were significantly reduced. Compliance was 93,4 %. The daily consumption of two servings of soft plain cheese was well accepted in terms of tastiness and appetite suited portion size. CONCLUSION: This randomized crossover controlled trial demonstrates that in elderly women living in nursing homes, the consumption of soft plain cheese increasing the supply of vitamin D, calcium and proteins, could reduce bone resorption and thereby reduce the risk of incidental fragility fractures in the long term.

Pubertal timing and body mass index gain from birth to maturity in relation with femoral neck BMD and distal tibia microstructure in healthy female subjects.

UNLABELLED: Childhood body mass index (BMI) gain is linked to hip fracture risk in elderly. In healthy girls, menarcheal age is inversely related to BMI gain during childhood and to femoral neck areal bone mass density (aBMD) and distal tibia structural components at maturity. This study underscores the importance of pubertal timing in age-related fragility fracture risk. INTRODUCTION: Recent data point to a relationship between BMI change during childhood and hip fracture risk in later life. We hypothesized that BMI development is linked to variation in pubertal timing as assessed by menarcheal age (MENA) which in turn, is related to peak bone mass (PBM) and hip fracture risk in elderly. METHODS: We studied in a 124 healthy female cohort the relationship between MENA and BMI from birth to maturity, and DXA-measured femoral neck (FN) aBMD at 20.4 year. At this age, we also measured bone strength related microstructure components of distal tibia by HR-pQCT. RESULTS: At 20.4 ± 0.6 year, FN aBMD (mg/cm(2)), cortical thickness (µm), and trabecular density (mg HA/cm(3)) of distal tibia were inversely related to MENA (P = 0.023, 0.015, and 0.041, respectively) and positively to BMI changes from 1.0 to 12.4 years (P = 0.031, 0.089, 0.016, respectively). Significant inverse (P < 0.022 to <0.001) correlations (R = -0.21 to -0.42) were found between MENA and BMI from 7.9 to 20.4 years, but neither at birth nor at 1.0 year. Linear regression indicated that MENA Z-score was inversely related to BMI changes not only from 1.0 to 12.4 years (R = -0.35, P = 0.001), but also from 1.0 to 8.9 years, (R = -0.24, P = 0.017), i.e., before pubertal maturation. CONCLUSION: BMI gain during childhood is associated with pubertal timing, which in turn, is correlated with several bone traits measured at PBM including FN aBMD, cortical thickness, and volumetric trabecular density of distal tibia. These data complement the reported relationship between childhood BMI gain and hip fracture risk in later life.

IOF position statement: vitamin D recommendations for older adults.

This position paper of the International Osteoporosis Foundation makes recommendations for vitamin D nutrition in elderly men and women from an evidence-based perspective.

Global vitamin D status and determinants of hypovitaminosis D.

UNLABELLED: This review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures. INTRODUCTION: Vitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders. The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and to identify the common and significant determinants of hypovitaminosis D. METHODS: Six regions of the world were reviewed-Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania-through a survey of published literature. RESULTS: The definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D, vary between studies. However, serum 25(OH)D levels below 75 nmol/L are prevalent in every region studied whilst levels below 25 nmol/L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main factors that are significantly associated with lower 25(OH)D levels. CONCLUSION: Reports from across the world indicate that hypovitaminosis D is widespread and is re-emerging as a major health problem globally.

The influence of pubertal timing on bone mass acquisition: a predetermined trajectory detectable five years before menarche.

BACKGROUND: Later menarcheal age (MENA) is a risk factor for osteoporosis. It is associated with low peak bone mass (PBM). Like PBM, MENA is under strong genetic influence. We hypothesized that MENA-related bone mass differences could be predetermined before puberty. METHODS: We tested this hypothesis in 124 healthy subjects followed from age 7.9 to 20.4 yr with dual-energy x-ray absorptiometry assessment at mean ages of 8.9, 10.0, 12.4, and 16.4 yr. Six sites were measured: radial metaphysis, radial diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4. Mean MENA (+/-SD) was 13.0 +/- 1.2 yr. The cohort was segregated by the median of MENA into LATER (14.0 +/- 0.7 yr) and EARLIER (12.1 +/- 0.7 yr) subgroups. RESULTS: At 20.4 +/- 0.6 yr, areal bone mineral density (aBMD) was lower in the LATER than the EARLIER subgroup at all six sites, with a mean difference of -0.31 Z-score (P = 0.022). Lower Z-scores in the LATER than in the EARLIER subgroup were observed at all sites at mean ages of 10.0, 12.4, and 16.4 yr, and before pubertal maturation, i.e. at 8.9 yr with a mean Z-score difference of -0.34 (P = 0.016). From mean age 8.9 to 20.4 yr, aBMD gains of all sites were similar in LATER and EARLIER subgroups, with mean of +301 and +308 mg/cm(2) (P = 0.402), respectively. CONCLUSIONS: In prepubertal girls who will experience later menarche, a deficit in aBMD can already be observed before the onset of pubertal maturation, with no further accumulated deficit until PBM compared to girls with earlier menarche. This suggests that shorter estrogen exposure from prepuberty to PBM is not the main factor for increased osteoporosis risk associated with later menarche. Rather common genetic determinants of low bone mass and later puberty could be involved.

Skeletal benefits from calcium supplementation are limited in children with calcium intakes near 800 mg daily.

INTRODUCTION AND HYPOTHESIS: Calcium supplementation enhances bone mass accrual during administration, with a sustained benefit observed using milk-based calcium but not calcium salts. We tested the hypothesis that calcium from milk minerals but not calcium carbonate will be sustained after supplementation was discontinued. METHODS: Ninety-nine pre-pubertal boys and girls aged 5-11 years were followed for 12 months after being randomized to receive 800 mg/day of calcium from milk minerals (MM) or calcium carbonate (CC), or a placebo (Pla) in a 10-month double blind study. Total body and regional BMC, and femoral shaft bone dimensions were measured using dual energy x-ray absorptiometry. Group differences were determined using ANCOVA. RESULTS: In the intention to treat analysis of the entire sample, no group differences were observed in increments in BMC or bone dimensions during or after supplementation. In those children who remained pre-pubertal, greater gains in pelvis BMC in the milk mineral group than controls were sustained (37.9 versus 29.3% respectively, p<0.02). CONCLUSION: In healthy children consuming about 800 mg calcium daily, calcium supplementation with milk minerals or calcium carbonate does not appear to be produce biologically meaningful benefits to skeletal health. A benefit of calcium supplementation in pre-pubertal was evident, but inconclusive, with the biological significance of the effect of calcium supplementation at the pelvis, and the longevity of this effect to be determined.

Skeletal site selectivity in the effects of calcium supplementation on areal bone mineral density gain: a randomized, double-blind, placebo-controlled trial in prepubertal boys.

BACKGROUND: Calcium supplementation during childhood and adolescence is considered an early means of preventing osteoporosis in adults. Prepuberty is an opportune time for detecting the benefits of calcium in girls. OBJECTIVE: The objective was to assess whether calcium supplementation increases bone mass gain in prepubertal boys in a skeletal site-specific manner. METHODS: In a 12-month double-blind, placebo-controlled trial with 1-yr follow-up, 235 healthy prepubertal boys aged 7.4 +/- 0.4 yr (mean +/- sd) were randomized to receive two food products providing 850 mg/d calcium (calcium supplement group, n = 116) or an isocaloric placebo (n = 119). Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry at radius (two sites), hip (two sites), femoral diaphysis (FDia), and L2-L4 vertebrae. RESULTS: At 12 months, aBMD gain was greater at the FDia and at the mean of the five appendicular skeletal sites in the calcium supplement group in both intention-to-treat analysis [76 +/- 32 vs. 64 +/- 33 mg/cm(2).yr; difference, 12.0 (95% confidence interval, CI, 3.6-20.3), P = 0.006; and 33 +/- 16 vs. 28 +/- 16 mg/cm(2).yr; difference, 5.1 (95% CI, 0.9-9.2); P = 0.018, respectively] and active treatment analysis [81 +/- 32 vs. 64 +/- 31 mg/cm(2).yr; difference, 17.2 (95% CI, 7.9-26.5); n = 174, P < 0.001; and 35 +/- 16 vs. 28 +/- 14 mg/cm(2).yr; difference, 7.5 (95% CI, 2.9-12.2); P = 0.002]. There was no beneficial effect of calcium on lumbar spine. The calcium effect was still detectable by ANOVA repeated measures analysis at the FDia (P = 0.004) and at the mean of the five appendicular skeletal sites (P = 0.002) 1 yr after the end of intervention (active treatment analysis). There was no change in bone size. CONCLUSION: In prepubertal boys, calcium-enriched foods increased aBMD at several appendicular skeleton sites, but not at the lumbar spine, and this without any bone size change. This effect was maintained 1 yr after treatment discontinuation.

Survival and potential years of life lost after hip fracture in men and age-matched women.

Hip fracture is associated with a higher mortality rate in men than in women. However, mean age of men and women with hip fracture differs markedly. Thus, some of the differences in the clinical pattern and outcome between genders could be related to different ages. To avoid the influence of age on gender-specific outcome, we analyzed prefracture conditions and hip fracture outcome in a cohort of men and of age-matched women. Risk factors for low bone mass were recorded in 106 men (mean age +/- SD, 80.3 +/- 9.3 years) and 264 age-matched women (mean age 81.4 +/- 8.0) with hip fracture. We compared mortality rate, survival, years of potential life lost and modification of housing conditions. These outcomes were prospectively assessed during an average 3.6 years follow-up (up to 7 years). Men with hip fracture differed from age-matched hip-fractured women by a higher alcohol and tobacco consumption, a greater frequency of living in couple, and by less prevalent fractures. Mortality rate after hip fracture was significantly higher in men (RR = 1.74, 95% CI 1.34-2.24). Since mortality is higher in the general male population, we compared reduction in life expectancy taking into account the gender-specific mortality rate. The excess mortality in each age-group of hip-fractured patients, which was measured during the whole follow-up period, and is an estimate of death attributable to fracture, did not differ between genders. Reduction in life expectancy due to hip fracture was similar in both genders (5.9 +/- 4.5 and 5.8 +/- 4.8 years, in men and women, respectively; NS), but the proportion of the years of life lost was higher in men (70 +/- 33%) than in women (59 +/- 42%, p < 0.01). It was concluded that for the same age, mortality rate after hip fracture was higher in men than in women. Although the reduction in life expectancy was similar in both genders, the proportion of the years of life lost was higher in men, suggesting a worse impact of hip fracture on survival in men, even after consideration of the higher mortality rate in the general male population.

An osteoporosis clinical pathway for the medical management of patients with low-trauma fracture.

Patients with an osteoporotic fracture have at least a 2-fold risk for additional fracture and should benefit from targeted diagnostic and treatment procedures for osteoporosis. To address this issue, we set up an osteoporosis clinical pathway (OCP) for the medical management of patients with low-trauma fracture. Following acute management of the fracture by the orthopedic team, patients are enrolled in the pathway, which is based on an interaction between the OCP multidisciplinary team, orthopedic surgeons and/or primary care physicians. After collection of patient data, suggestions for additional diagnostic examinations with their interpretation, and treatment proposals are made. Patients and their families are also invited to attend a multidisciplinary interactive educational program on physical therapy, lifestyle habits and nutrition. During a 36-month period, 385 patients (311 women, 74 men; mean age +/- SD: 73.0 +/- 13.5 years; hip fracture 45%, ankle/tibia 24%, proximal humerus 8.6%, spine 5.5%, pelvis 3.9%, distal forearm 3.6%, other sites 17.4%) were enrolled in the OCP. An osteoporosis awareness questionnaire administered within 10 days of fracture showed that 73% of patients believed that their fracture was not related to the disease. Dual-energy X-ray absorptiometry, performed in 63% of patients, showed that 86% had low bone mass or osteoporosis. Specific antiosteoporotic therapy was proposed for 33% of patients in addition to calcium and vitamin D supplements, the latter suggested for 93%. A survey performed in 216 patients 6 months later, indicated that 63% of the suggested treatments had been prescribed and that 67% of this group were continuing treatment. Such a clinical pathway for the medical management of low-trauma fracture can help to identify patients with osteoporosis in a high-risk population, provide support to the orthopedic surgeon and/or the primary care physician for diagnostic and treatment procedures, and should significantly contribute to increase awareness of the disease in patients and their families.

Dietary essential amino acid supplements increase bone strength by influencing bone mass and bone microarchitecture in ovariectomized adult rats fed an isocaloric low-protein diet.

This study was designed to investigate whether the administration of dietary essential amino acid supplements in adult rats made osteoporotic by estrogen deficiency and reduced protein intake could reverse the deleterious effects caused by these maneuvers. This animal model was selected to mimic the situation observed in elderly women in whom estrogen deficiency and/or low-protein intake (but also calcium and vitamin D deficiency) are known to contribute to the pathogenesis of osteoporosis. Six-month-old rats were ovariectomized (OVX) and fed an isocaloric 2.5% casein diet for 10 weeks or sham-operated (SHAM) and fed an isocaloric 15% casein diet. The animals fed the 2.5% casein diet were given isocaloric supplements of essential amino acids in similar relative proportion to that of casein at doses of 2.5% or 5% of total diet for an additional 16 weeks. Vertebrae, femur, and tibia bone mineral density (BMD); ultimate strength; and microtomographic histomorphometry were evaluated before and after dietary essential amino acid supplements. Essential amino acid supplements increased vertebrae, femur, and tibia bone strength in OVX rats fed a low-protein diet. The mechanical changes induced by this dietary isocaloric supplement were associated with the prevention of a further BMD decrease or even with some increases and changes in microarchitecture such as from a rod to a plate trabecular spacial configuration and increased cortical thickness. Higher insulin-like growth factor (IGF) I levels, as well as greater bone formation and reduced bone resorption as assessed by biochemical markers of bone remodeling, were found in rats receiving essential amino acid supplements. In conclusion, dietary essential amino acid supplements increased bone strength through modifications of BMD, trabecular architecture, and cortical thickness possibly by an IGF-I-mediated process.

Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation.

In the present study, we investigate the implication of the mitogen-activated protein kinases (MAPKs) Erk, p38, and JNK in mediating the effect of fetal calf serum (FCS) on the differentiation of MC3T3-E1 osteoblast-like cells. Erk is stimulated by FCS in proliferating, early-differentiating, as well as in mature cells. Activation of p38 by FCS is not detected in proliferating cells but is observed as the cells differentiate. JNK is activated in response to FCS throughout the entire differentiation process, but a maximal stimulation is observed in early differentiating cells. The roles of Erk and p38 pathways in mediating MC3T3-E1 cell differentiation was determined using specific inhibitors such as U0126 and SB203580, respectively. These experiments confirmed that the Erk pathway is essential for mediating cell proliferation in response to FCS, but indicated that this MAP kinase has little effect in regulating the differentiation of MC3T3-E1 cells. In contrast, p38 only marginally influenced proliferation, but appeared to be critical for the control of alkaline phosphatase (ALP) expression in differentiating cells. Finally, results obtained with high doses of SB203580, which also affected JNK activity, suggest that p38 and/or JNK are probably also involved in the control of type 1 collagen and osteocalcin expression in differentiating cells. The data indicate that MAPKs regulate different stages of MC3T3-E1 cell development in response to FCS. Distinct MAPK pathways seem to independently modulate osteoblastic cell proliferation and differentiation, with Erk playing an essential role in cell replication, whereas p38 is involved in the regulation of ALP expression during osteoblastic cell differentiation. JNK is also probably involved in the regulation of osteoblastic cell differentiation, but its precise role requires further investigation.