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Gonadal failure induces bone loss while obesity prevents it. This raises the possibility that bone mass, body weight, and gonadal function are regulated by common pathways. To test this hypothesis, we studied leptin-deficient and leptin receptor-deficient mice that are obese and hypogonadic. Both mutant mice have an increased bone formation leading to high(More)
1,25-Dihydroxyvitamin D3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were(More)
The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast(More)
The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression is restricted to the parathyroid glands. Here we show that(More)
The clinical relevance and nature of calcaneal cysts is controversial. The risk of pathologic fracture is undefined and diagnostic criteria to differentiate between cysts in patients who can be treated nonoperatively and patients who require surgical intervention are not available. To address these questions, 50 calcaneal bone cysts in 47 patients were(More)
Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high(More)
Calcitonin (CT) is a known inhibitor of bone resorption. Calcitonin gene-related peptide-alpha (CGRPalpha), produced by alternative RNA processing of the CT/CGRP gene, has no clearly defined role in bone. To better understand the physiologic role of the CT/CGRP gene we created a mouse in which the coding sequences for both CT and CGRPalpha were deleted by(More)
The critical role of c-src in osteoclast-mediated bone resorption has been emphasized by gene deletion experiments in mice. However, the long-term effects of the lack of c-src and impaired osteoclast function on the skeleton remain unknown. To further study the physiological role of c-src and to circumvent the early death of src(-/-) mice, due to starvation(More)
Strontium ranelate (SR) is one therapeutic option for reducing risk of fracture in osteoporosis. The effects of SR treatment on hydroxyapatite (HA) previously altered by bisphosphonate (BP) administration remain to be established. Patients who have received long-term BP treatment and present with persistent high fracture risk are of particular interest.(More)