CXXC5 is a negative-feedback regulator of the Wnt/ß-catenin pathway involved in osteoblast differentiation.

The positive roles of the Wnt/ß-catenin pathway in osteoblast differentiation and bone mineral density (BMD) maintenance have been clearly demonstrated in both animal experiments and clinical investigations. CXXC finger protein 5 (CXXC5), a recently identified negative regulator of the Wnt/ß-catenin pathway, showed altered cellular localization and function, which were dependent on the cell type in previous studies. However, the in vivo function of CXXC5 has not been clearly investigated yet. Here, we characterized CXXC5 as a negative regulator of osteoblast differentiation and bone formation. Deficiency of CXXC5 resulted in elevated BMD in mice without any severe gross developmental abnormalities. CXXC5 exerted a negative-feedback effect on the Wnt/ß-catenin pathway via Wnt-dependent binding to Dishevelled (Dvl) during osteoblast differentiation. Suppression of the Dvl-CXXC5 interaction using a competitor peptide resulted in the activation of the Wnt/ß-catenin pathway and osteoblast differentiation, and accelerated thickness growth of ex vivo-cultured calvariae. Overall, CXXC5 is a negative-feedback regulator induced by Wnt/ß-catenin signaling that inhibits osteoblast differentiation and bone formation via interaction with Dvl.

Gender-specific pleiotropic bone-muscle relationship in the elderly from a nationwide survey (KNHANES IV).

SUMMARY: The aim of this study was to examine the gender-specific association between sarcopenia and bone geometry/metabolic parameters. Low muscle mass was associated with greater deterioration of bone than in deterioration of glucose or lipid profiles. This bone-muscle relationship was more prominent in men than in women. INTRODUCTION: There are few studies that report on gender differences in the effects of low muscle mass on bone and metabolic parameters in elderly subjects. This study aimed to assess the gender-specific influence of muscle mass on bone and metabolic parameters. METHODS: A total of 2,264 participants (940 men and 1,324 women) whose age ranged from 65 to 92 years were analyzed using data from The Fourth Korea National Health and Nutrition Examination Surveys (2008-2009). We measured bone mineral density (BMD) and appendicular muscle mass using the dual-energy X-ray absorptiometry and also measured metabolic profiles. RESULTS: The age-related trend in bone and muscle coincided in men but not in women. Femoral neck (FN) and total hip (TH) BMD were highly correlated with muscle mass in both genders. However, in women, this correlation was not significant in the lumbar spine (LS). In addition, this positive correlation was stronger in the FN or TH than in the LS and was stronger in men than in women. Subjects with sarcopenia were at a higher risk for osteoporosis in the FN, TH, and LS in men, and in the TH and FN in women. The degree of association between muscle mass and metabolic profiles was relatively very weak. CONCLUSION: Bone-muscle relationship was more prominent in men than in women. The gender differences in bone-muscle relationship may be helpful for the development of gender-specific preventive strategies in the elderly, especially in men.

Osteonecrosis of the jaw induced by oral administration of bisphosphonates in Asian population: five cases.

SUMMARY: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) can occur irrespective of race. Old age and long-term use of corticosteroid may be a more reliable risk factor than racial characteristics. INTRODUCTION: BRONJ is an increasingly common problem. Most BRONJ occurs following an intravenous administration of bisphosphonate treatment for malignant bone disease and metastatic cancer. As the incidence of BRONJ caused by oral administration of bisphosphonate is quite low, it is believed that this medication is relatively safe and effective in preventing complications of osteoporosis, such as hip or spine fractures. The many known risk factors for BRONJ can be classified as drug-related, local, demographic, and systemic. One demographic and systemic risk factor is race. Most of the case reports of BRONJ present elderly, white women. METHODS: In this report, we describe five cases of BRONJ caused by oral administration of bisphosphonate in Asian population. RESULTS: All the patients were female and over 65 years old. Three patients had been prescribed with corticosteroids for rheumatoid arthritis. CONCLUSION: Irrespective of race, elderly women undergoing steroid therapy have an increased incidence of BRONJ even with oral administration of bisphosphonate.