Osteoporosis is one of the most common degenerative diseases. It is characterized by reduced bone mineral density (BMD) with an increased risk for bone fractures. There is a substantial genetic contribution to BMD, although the genetic factors involved in the pathogenesis of human osteoporosis are largely unknown. Mice with a targeted deletion of either the cannabinoid receptor type 1 (Cnr1) or type 2 (Cnr2) gene show an alteration of bone mass, and pharmacological modification of both receptors can regulate osteoclast activity and BMD. We therefore analyzed both genes in a systematic genetic association study in a human sample of postmenopausal osteoporosis patients and matched female controls. We found a significant association of single polymorphisms (P=0.0014) and haplotypes (P=0.0001) encompassing the CNR2 gene on human chromosome 1p36, whereas we found no convincing association for CNR1. These results demonstrate a role for the peripherally expressed CB2 receptor in the etiology of osteoporosis and provide an interesting novel therapeutical target for this severe and common disease.

Background. End-stage renal disease is often associated with altered bone metabolism. Methods. In order to investigate the determinant factors of bone mineral density (BMD) and the risk factors of fractures, we studied 70 patients; 26 women (23 post-menopausal) and 44 men, (mean±SD) aged 60.5±14.3 years, treated by standard haemodialysis (HD) for 6.4±6.8 years. Main circulating bone biochemical markers were assessed and BMD was measured with a Lunar DPX densitometer at five sites. BMD results are expressed as a function of age and gender (Z-score). Results. Mean Z-score was markedly decreased at the mid-radius (−2.75±1.23) whereas it was normal at the femoral neck (−0.42±1.13) and lumbar spine (0.02±2.13), and total body (−0.62±1.53). Time on HD was negatively correlated to the Z-score at the mid-radius and total body but not at the other sites. Serum intact parathyroid hormone (iPTH), whole PTH or cyclase activating PTH (CAP) and bone-specific alkaline phosphatase concentrations were negatively correlated with Z-scores at all sites. Twenty-one out of 70 patients had sustained a total of 27 fractures since the beginning of dialysis therapy (seven ribs, seven ankles, six vertebrae, three humerus, two wrists and two hips). They had a total body Z-score significantly lower than that of patients without fractures, −1.34±1.54 vs −0.37±1.46, respectively (P<0.031); however, their Z-scores at the other sites were not different. They were on HD for longer time, 10.4±9.5 vs 5.0±5.1, respectively (P<0.003), and the relative risk of skeletal fractures was 6.4 times greater after 10 years of HD. The seven patients with rib fractures had a decreased Z-score at most of the sites but not at the mid-radius. Rib fractures but no other fractures were associated with markedly decreased body weight, fat mass and serum leptin levels. Conclusions. In conclusion, the Z-score at the mid-radius was decreased in HD patients and correlated with high serum PTH but not with fractures. Bone fractures were associated with the time passed on HD and with a low total body Z-score. Rib fractures were frequent and associated with a poor nutritional state.

Osteoporosis has be reported to be a complication of active antiretroviral therapy of HIV infection. We studied 148 HIV‐infected men stratified according to their treatment. Our data show that these patients have an average 9% decreased BMD, irrespective of their treatment. Low body mass index and high resorption markers were associated with low bone density. Introduction: Osteoporosis has been reported in HIV‐infected (HIV⁺) patients, and it has been suggested that it may be linked to protease‐inhibitor treatments (PI). Materials and Methods: To assess this risk and to investigate its putative link with treatments, we compared the bone density of HIV⁺ men, who were either receiving treatment (including PI [PI⁺], n = 49; without PI [PI⁻], n = 51) or untreated (UT, n = 48). We included 81 age‐matched control HIV‐negative (HIV⁻) males (age, 40 ± 8 years). Results: BMD adjusted for age (Z‐score) was lower in the HIV⁺ patients at the lumbar spine (HIV⁺: −1.08 ± 1.21, HIV⁻: −0.06 ± 1.26, p < 0.001) and the femoral neck (HIV⁺: −0.39 ± 1.05, HIV⁻: 0.25 ± 0.87, p < 0.001). The prevalence of osteoporosis was 16% in HIV⁺ and 4% in HIV⁻ subjects (p < 0.01). In the HIV⁺ subjects, the Z‐score was correlated only to body mass index (r = 0.27 at lumbar spine and 0.35 at femoral neck). Untreated HIV⁺ patients had a negative Z‐score (−0.82 ± 1.15 for the lumbar spine), which was not different from the one of treated HIV⁺ patients. In the PI⁺ and PI⁻ groups, the Z‐score did not depend on the presence of lipodystrophy or the proportion of fat in the abdomen and legs measured by DXA. Markers of bone remodeling were measured in the 132 HIV⁺ and 35 HIV⁻ subjects. Compared with controls, HIV⁺ patients had lower bone alkaline phosphatase and higher urinary cross‐laps/Cr, which was negatively correlated with the Z‐score at both the femoral neck (r = −0.22) and lumbar spine (r = −0.21). TNFα was increased in untreated compared with treated HIV⁺ subjects and was not correlated to the Z‐score. Conclusion: Our cross‐sectional study does not show any deleterious effect of the treatment but does indicate a decrease in bone density in HIV⁺ patients irrespective of the treatment. This low bone density is in part related to the low body weight and is associated with increased bone resorption.