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Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20 mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-mo treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20 mg/kg open label. Therefore, only results from the 2, 8, and 20 mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular volumetric bone mineral density (vBMD) from baseline at month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro-finite element (microFE)-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12 mo, there was a significant increase in mean (SE) failure load in the 20 mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20 mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p>05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20 mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Adding to its well-known roles in locomotion and calcium balance, the skeleton has recently been appreciated as a true endocrine organ. Bone remodeling, a highly dynamic process, requires synchronized activities and crosstalk between bone cells. Discovery and characterization of the Wnt/β catenin pathway in bone formation, FGF23 regulation of phosphate homeostasis and osteocalcin in energy and glucose homeostasis have reframed our view of the skeleton from simply a target tissue of the endocrine system to an endocrine tissue itself. This comprehensive review provides an overview of these complex pathways, their application to human bone disorders and implications for developing diagnostic and therapeutic targets.

The Clinician's Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.

Ascites is a rare but important complication of hypothyroidism. Because of the rarity of the disease and the inconsistency of symptoms associated with hypothyroidism, patients often go undiagnosed for months. Institution of thyroid replacement hormone results in rapid and complete resolution of ascites. Here we present a case of myxedema ascites that presented in a 52-year-old man 4 months after allogeneic bone marrow transplant (BMT). Diagnoses initially considered in the differential included the common post-BMT complications, namely, hepatic veno-occlusive disease, graft vs. host disease, and infection. However, posttransplant patients are also at risk for illnesses unrelated to their underlying diagnosis or transplant procedure, including hypothyroidism. This case illustrates the importance of considering a broad differential diagnosis in posttransplant patients, especially those in whom the clinical course is atypical., (Copyright 2002 Wiley-Liss, Inc.)