Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family of proteins and plays an important role in the negative regulation of osteoclastic bone resorption. Whether OPG/OCIF circulates in human blood and how its level changes under pathological conditions is not known. To address these issues, a panel of monoclonal antibodies was generated against recombinant OPG/OCIF and screened for reactivity with solid-phase monomeric and homodimeric forms of the recombinant protein. Antibodies that showed high affinity for both forms of OPG/OCIF and those that selectively recognized the homodimer were identified, enabling development of two types of sensitive enzyme-linked immunosorbent assay (ELISA): one that detects both forms of OPG/OCIF equally and one specific for the homodimer. Characterization of circulating OPG/OCIF with these ELISAs revealed that the protein exists in human serum mainly in the monomeric form. The serum concentration of OPG/OCIF increased with age in both healthy Japanese men and women, and was significantly higher in postmenopausal women with osteoporosis than in age-matched controls. Within the osteoporotic group, serum OPG/OCIF concentrations were higher in patients with low bone mass. Serum OPG/OCIF concentrations were also significantly increased in those postmenopausal women with a high rate of bone turnover, as determined by increased serum bone-specific alkaline phosphatase and urinary excretion of pyridinoline and deoxypyridinoline. The results suggested that circulating OPG/OCIF levels are regulated by an age-related factor(s) and that the increased serum concentration may reflect a compensative response to enhanced osteoclastic bone resorption and the resultant bone loss rather than a cause of osteoporosis. (J Bone Miner Res 1999;14:518-527)

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This study showed a higher prevalence of sarcopenia and more reduced leg muscle mass in patients after a hip fracture than in the outclinic patients who did not have hip fractures. The results imply sarcopenia can be a risk factor for a hip fracture.

Transforming growth factor-␤ (TGF-␤) is both abundant in bone and an important regulator of bone metabolism. A T3 C transition at nucleotide 29 in the signal sequence region of the TGF-␤1 gene results in a Leu3 Pro substitution at amino acid position 10. The possible association of this polymorphism with bone mass and the prevalence of osteoporosis has now been investigated in a total of 287 postmenopausal women from two regions (Obu City, Aichi Prefecture, and Sanda City, Hyogo Prefecture) of Japan. A significant association of TGF-␤1 genotype with bone mass was detected in both populations; bone mineral density (BMD) at the lumbar spine was greater in individuals with the CC genotype than in those with the TT or TC genotype. The frequency of vertebral fractures was significantly lower in individuals with the CC genotype than in those with the TC or TT genotypes. For each region, multivariable logistic regression analysis revealed that the frequency of the T allele was significantly higher in subjects with osteoporosis than in controls. Also, the serum concentration of TGF-␤1 in individuals with the CC genotype was significantly higher than that in age-matched subjects with the TC or TT genotype in osteoporotic or osteopenic as well as healthy control groups. These results suggest that the T/C polymorphism of the TGF-␤1 gene is one of the genetic determinants of bone mass and that the T allele is an independent risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women. Thus, analysis of the TGF-␤1 genotype may be useful in the prevention and management of osteoporosis. (J Bone Miner Res 1998;13:1569-1576)

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We found higher prevalence of sarcopenia and lower leg muscle mass among patients with acute OVF compared with patients who did not have an OVF. These results suggest that sarcopenia may be a risk factor for OVF.

A drastic increase occurred in the number of patients with hip fractures with time in Japan. One problem in the treatment of hip fractures is the long waiting time from hospitalization to surgery resulting from difficulties in securing operating rooms.

ObjectivesThe prevalence of chronic low back pain (CLBP) increases with age and several mechanisms are involved in the development of CLBP, including osteoporosis; however, no associations with sarcopenia have yet been identified.MethodsIn total, 100 patients with CLBP and 560 patients without CLBP (nCLBP) aged over 65 years were studied. Skeletal muscle mass index (SMI) and percentage of body fat were evaluated using whole-body dual-energy X-ray absorptiometry. Sarcopenia was diagnosed when the relative SMI was more than 2 standard deviations below the mean in young adults. Thus, the cutoff value for sarcopenia was defined according to Sanada's Japanese population data. Paraspinal muscle cross-sectional areas of the lumbar multifidus and the erector spinae muscles were calculated using magnetic resonance imaging.ResultsForty patients (40.0%) from the CLBP group and 149 (26.6%) from the nCLBP group met the criteria of sarcopenia. SMI was significantly lower and the body fat ratio was significantly higher in the CLBP group compared with the nCLBP group. Sarcopenic obesity was significantly observed in the CLBP group. Lumbar multifidus and the erector spinae muscle cross sectional area were significantly lower in the CLBP group.ConclusionsElderly patients with CLBP have significantly lower skeletal muscle mass, and age-related mechanisms in sarcopenia are considered to be associated with chronic pain. Therapeutic procedures that are used to treat elderly aging muscle, including muscle strengthening and performance training, can possibly be a treatment for or used to prevent elderly CLBP.