Thierry Chevalley

Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients

The efficacy of calcium (Ca) in reducing bone loss is debated. In a randomized placebo-controlled double-masked study, we investigated the effects of oral Ca supplements on femoral shaft (FS), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD), and on the incidence of vertebral fracture in vitamin-D-replete elderly. Ninety-three healthy subjects (72.1±0.6 years) were randomly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months. Sixty-three patients (78.4±1.0 years) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo. FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group (+0.6±0.5% v −1.2±0.7%,p<0.05). There was no difference in effect between the two forms of Ca. The changes of +0.7±0.8% v −1.7±1.6% in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance. In fractured patients, FS, FN and LS BMD changes were −1.3±0.8, +0.3±1.6 and +3.1±1.2% (p<0.05 for the last). The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group, respectively, and 144.0 in Ca-supplemented fractured patients. Thus, oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly.

Vitamin-D-receptor-gene polymorphisms and change in lumbar-spine bone mineral density.

Common vitamin-D-receptor (VDR) gene allelic variants predict bone mineral density. We analysed VDR alleles and rate of change of lumbar-spine bone mineral density over 18 months in 72 elderly subjects. 9 BB homozygotes lost bone mineral density but 26 homozygotes for the alternative genotype (bb) did not (mean change -2.3 [SE 1.0] vs 0.9 [0.7]% per year, p < 0.05), irrespective of calcium intake. Among 37 heterozygotes (Bb), however, change in bone mineral density correlated with calcium intake (r = 0.35, p < 0.03). This association between a genetic marker and rate of bone loss in the elderly suggests that the effect of calcium intake on maintenance of bone mass could relate to VDR gene polymorphisms.

Gain in bone mineral mass in prepubertal girls 3–5 years after discontinuation of calcium supplementation: a follow-up study

BACKGROUND Calcium supplementation during childhood and adolescence increases bone-mass accrual. Whether or not this benefit persists after discontinuation of supplementation is not known. We previously showed a favourable effect of milk-extracted calcium phosphate incorporated in various foods on accumulation of bone mineral mass in 8-year-old girls. We now report the results of a follow-up study undertaken more than 3 years after the end of calcium supplementation. METHODS Anthropometric and bone variables were measured in 116 of the 144 girls whose data had been studied at the end of the supplementation period. The mean time elapsed between the end of the intervention period and this follow-up measurement was 3.5 years. Areal bone mineral density was measured by dual-energy X-ray absorptiometry at the same six skeletal sites as those studied during the intervention phase. FINDINGS We were able to remeasure 62 and 54 girls of the calcium-supplemented and placebo groups, respectively. The increase from baseline in the overall mean bone mineral density of the six skeletal sites was still highly significant (calcium-supplemented group 179 mg/cm(2) [SE 8] vs placebo group 151 mg/cm(2) [7], p=0.012). A significant difference in favour of the supplemented group was also seen with respect to mean bone mineral content (p=0.031) and mean bone area (p=0.04). Difference in pubertal maturation did not seem to account for the recorded differences. INTERPRETATION Our results suggest that this form of milk-extracted calcium phosphate taken during the prepubertal period can modify the trajectory of bone mass growth and cause a long-standing increase in bone mass accrual, which lasts beyond the end of supplementation.

An Osteoporosis Clinical Pathway for the Medical Management of Patients with Low-Trauma Fracture

Abstract: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.

Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility.

Preferential low bone mineral density of the femoral neck in patients with a recent fracture of the proximal femur

Bone mass is an important determinant of resistance to fractures. Whether bone mineral density (BMD) in subjects with a fracture of the proximal femur (hip fracture) is different from that of age-matched controls is still debated. We measured BMD of the femoral neck (FN) on the opposite side to the fracture, as well as femoral shaft (FS) and lumbar spine (LS) BMD by dual-photon absorptiometry in 68 patients (57 women and 11 men, mean age 78.8±1.0) 12.4±0.8 days after hip fracture following a moderate trauma. These values were compared with BMD of 93 non-fractured elderly control subjects (82 women and 11 men), measured during the same period. As compared with the controls, FN BMD was significantly lower in fractured women (0.592±0.013 v. 0.728±0.014 g/cm2,P<0.001) and in fractured men (0.697±0.029 v. 0.840±0.052,P<0.05). Expressed as standard deviations above or below the mean BMD of age and sex-matched normal subjects (Z-score), the difference in FN BMD between fractured women and controls was highly significant (−0.6±0.1 v. +0.1±0.1,P<0.001). As compared with mean BMD of young normal subjects, BMD was decreased by 36.9±1.4 and 22.4±1.5% (P<0.001) in fractured and control women, respectively. There was no significant difference between FN BMD of 33 women with cervical and 24 with trochanteric hip fractures (0.603±0.017 v. 0.577±0.020). FN BMD was lower than 0.705 g/cm2 in 90% of fractured women. The prevalence of fracture increased with decreasing FN BMD, reaching 100% with values below 0.500 g/cm2. FS and LS BMD were significantly lower in women with hip fracture than in controls (1.388±0.036 v. 1.580±0.030,P<0.001, for FS, and 0.886±0.027 v. 0.985±0.023,P<0.01, for LS), but these differences were not significant when expressed as a Z-score. In men with a recent hip fracture, FS BMD was significantly lower than in controls (1.729±0.096 v. 2.069±0.062,P<0.01), but the difference at the LS level did not reach statistical significance. These results indicate that both women and men with a recent hip fracture had decreased bone mineral density of the femoral neck, femoral shaft and lumbar spine. However, the difference appeared to be of higher magnitude for the femoral neck suggesting a preferential bone loss at this site.

High-protein intake enhances the positive impact of physical activity on BMC in prepubertal boys

In 232 healthy prepubertal boys, increased physical activity was associated with greater BMC at both axial and appendicular sites under high‐protein intake.

Protein intake, IGF-1 and osteoporosis

Deficiency in nutritional elements could play an important role in the pathogenesis of osteoporotic fracture in the elderly. Results of several studies indicate that calcium supplementation reduces bone loss and fracture incidence in vitamin D replete elderly subjects [1]. Other investigations have suggested that the level of protein intake could influence either calcium phosphate metabolism, bone mass or the risk of osteoporotic fracture [2]. Apparently contradictory information suggests that either a deficient or an excessive protein supplement could negatively affect the balance of calcium and the arnount of bony tissue contained in the skeleton [2,3]. Several reasons can be evoked with respect to the present uncertainty regarding the effect of protein supplementation on calcium balance and bone mass. The outcomes may differ because the protein supplementation was: (a) prescribed either to wellnourished people or to subjects exhibiting signs of malnutrition; (b) given in various forms: natural food products (i.e. ingested in complex forms), purified extracts or mixtures of amino acids; (c) of either animal (e.g. casein) or vegetable (e.g. soya) origin; (d) evaluated over either the short term or the long term; (e) assessed in the presence or absence of modifications in other nutritional factors such as energy and/or calcium. The recommended daily allowance (RDA) for protein varies from 2.0 g/kg body weight in children to 1.0 g/kg in adolescents, and 0.75 g/kg in adults [4]. Protein intake below the RDA could be particularly detrimental for both the acquisition of bone mass and the conservation of bone integrity with aging. Protein undemutrition during childhood and adolescence results in a reduction of height, weight and overall body protein [5] and, therefore, can be expected to affect peak bone mass. A sufficient protein intake is also mandatory for the maintenance of bone homeostasis during adulthood. In the elderly, malnutrition can be considered as a risk factor for hip fracture because it can accelerate age-

Evaluation of the Age-Adjusted Incidence of Hip Fractures Between Urban and Rural Areas: The Difference Is Not Related to the Prevalence of Institutions for the Elderly

Abstract: As many as 40% of hip fractures occur in institutions for the elderly. Several studies have demonstrated a higher age-adjusted incidence of hip fractures in urban areas compared with rural areas. To assess whether this difference could be due to a preferential location of institutions for the elderly in urban areas, we compared the incidence of hip fractures over a 5-year period in urban versus rural areas, as defined according to the population density (urban >15 inhabitants/ha2). We then determined the age-adjusted incidence of hip fractures in institutional-dwelling elderly and home-dwelling elderly. Hip fracture incidence was 100.0/100 000 (150.5 in women and 43.8 in men) in urban areas, and 71.0/100 000 (107.2 in women and 32.8 in men) in rural areas (p<0.001). When only those patients living in their own homes were analyzed, the incidence was 66.7/100 000 (94.6 in women and 35.7 in men) in urban regions and 36.8/100 000 (49.6 in women and 23.4 in men) in rural areas (p<0.001), a difference of even greater magnitude than when both home-dwelling and institutional-dwelling residents were considered together. In a logistic regression model including age class, gender, urban or rural areas and institutionalization for inhabitants 65 years of age and older, urban residents have a 31% significantly (p<0.001) higher incidence of hip fracture compared with rural residents; women have a 79% significantly (p<0.001) higher incidence of hip fracture compared with men; and institutional-dwelling elderly have a 351% significantly (p<0.001) higher incidence of hip fracture compared with home-dwelling elderly. These results confirm the existence of a higher age-adjusted incidence of hip fractures in urban compared with rural areas. Since this difference is increased when patients living at home were analyzed separately, it indicates that the difference between urban and rural areas is not due to a preferential urban location of institutions for the elderly.

Influence of age at menarche on forearm bone microstructure in healthy young women.

BACKGROUND Shorter estrogen exposure from puberty onset to peak bone mass attainment may explain how late menarche is a risk factor for osteoporosis. The influence of menarcheal age (MENA) on peak bone mass, cortical, and trabecular microstructure was studied in 124 healthy women aged 20.4 +/- 0.6 (sd) yr. METHODS At distal radius, areal bone mineral density (aBMD) was measured by dual-energy x-ray absorptiometry, and volumetric bone mineral density (BMD) and microstructure were measured by high-resolution peripheral computerized tomography, including: total, cortical, and trabecular volumetric BMD and fraction; trabecular number, thickness, and spacing; cortical thickness (CTh); and cross-sectional area (CSA). RESULTS Median MENA was 12.9 yr. Mean aBMD T score of the whole cohort was slightly positive. aBMD was inversely correlated to MENA for total radius (R = -0.21; P = 0.018), diaphysis (R = -0.18; P = 0.043), and metaphysis (R = -0.19; P = 0.031). Subjects with MENA more than the median [LATER: 14.0 +/- 0.7 (+/-sd) yr] had lower aBMD than those with MENA less than the median (EARLIER: 12.1 +/- 0.7 yr) in total radius (P = 0.026), diaphysis (P = 0.042), and metaphysis (P = 0.046). LATER vs. EARLIER displayed lower total volumetric BMD (315 +/- 54 vs. 341 +/- 56 mg HA/cm(3); P = 0.010), cortical volumetric BMD (874 +/- 49 vs. 901 +/- 44 mg HA/cm(3); P = 0.003), and CTh (774 +/- 170 vs. 849 +/- 191 microm; P = 0.023). CTh was inversely related to CSA (R = -0.46; P < 0.001). In LATER reduced CTh was associated with 5% increased CSA. CONCLUSIONS In healthy young adult women, a 1.9-yr difference in mean MENA was associated with lower radial aBMD T score, lower CTh without reduced CSA, a finding compatible with less endocortical accrual. It may explain how late menarche is a risk factor for forearm osteoporosis.