Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin.

Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult Postn(-/-) and Postn(+/+) mice to intermittent PTH.

Inhibition of T cell-dependent and RANKL-dependent osteoclastogenic processes associated with high levels of bone mass in interleukin-15 receptor-deficient mice.

Objective: T cell production of RANKL, interferon-γ (IFNγ), and other cytokines in inflammatory processes such as rheumatoid arthritis or secondary to conditions such as estrogen deficiency stimulates osteoclast activity, which leads to bone resorption and bone loss. The purpose of this study was to characterize the effects of interleukin-15 (IL-15), a master T cell growth factor whose role in bone remodeling remains unknown.

Methods: We used mice lacking the IL-15 receptor (IL-15Rα(-/-) ) to investigate the effects of IL-15 on osteoclast development, T cell and dendritic cell activation in vitro and in vivo, bone mass, and microarchitecture in intact and ovariectomized (OVX) mice.

Beta-arrestin-biased parathyroid hormone ligands: a new approach to the development of agents that stimulate bone formation.

Because daily treatment with parathyroid hormone (PTH) increases bone mass and decreases fracture risk, physicians use this agent to treat osteoporosis. However, PTH stimulates both bone-forming and bone-resorbing cells, complicating its clinical use. New results show that, in mice, a so-called biased agonist (PTH-betaarr) that selectively activates beta-arrestin -dependent signaling leads to PTH-induced trabecular bone formation without a simultaneous increase in bone resorption.

The matricellular protein periostin is required for sost inhibition and the anabolic response to mechanical loading and physical activity.

Periostin (gene Postn) is a secreted extracellular matrix protein involved in cell recruitment and adhesion and plays an important role in odontogenesis. In bone, periostin is preferentially expressed in the periosteum, but its functional significance remains unclear. We investigated Postn(-/-) mice and their wild type littermates to elucidate the role of periostin in the skeletal response to moderate physical activity and direct axial compression of the tibia.

The role of calcium and vitamin D in the management of osteoporosis.

The role of calcium and vitamin D supplementation in the treatment of osteoporosis has been extensively studied. The aim of this paper was to reach, where possible, consensus views on five key questions relating to calcium and vitamin D supplementation in the management of osteoporosis. Whereas global strategies that target supplementation to the general population could not be justified in terms of efficacy and health economics, there is a clearer rationale for supplementing patients who are at increased risk of osteoporosis and those who have developed osteoporosis, including those already taking other treatments for osteoporosis.

Osteoporosis: non-hormonal treatment.

Significant progress has been achieved in osteoporosis treatment, in terms of agents with novel mechanisms of action, of new schedules of administration, and of long-term treatment safety demonstration. Alendronate, ibandronate, intranasal calcitonin, parathyroid hormones, raloxifene, risedronate, hormone replacement therapy, strontium ranelate and zoledronate decrease the risk of vertebral fracture. Alendronate, risedronate, strontium ranelate and zoledronate reduce the risk of hip fracture in women with osteoporosis, hormone replacement therapy in postmenopausal women, and calcium and vitamin D in institutionalized patients.

Bone mass in prepubertal boys is associated with a Gln223Arg amino acid substitution in the leptin receptor.

Objective: The contribution of leptin to bone mass acquisition in humans remains unclear. We investigated the association of the Gln223Arg polymorphism in the leptin receptor gene (LEPR) with bone mineral content (BMC) and areal bone mineral density (aBMD) in prepubertal boys and LEPR interaction with vitamin D receptor (VDR) genotypes (Bsm1 and Fok1).

Design: In a cross-sectional design with a longitudinal follow-up, dual-energy x-ray absorptiometry measurements at the lumbar spine, hip, femoral diaphysis, and radius were performed at baseline (mean age 7.

Bone response to intermittent parathyroid hormone is altered in mice null for {beta}-Arrestin2.

Intermittent PTH administration increases bone turnover, resulting in net anabolic effects on bone. These effects are primarily mediated by intracellular cAMP signaling. However, the molecular mechanisms that regulate PTH activity in bone remain incompletely understood.

Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats.

Unlabelled: Strontium ranelate given to intact rats at doses up to 900 mg/kg/day increases bone resistance, cortical and trabecular bone volume, micro-architecture, bone mass, and total ALP activity, thus indicating a bone-forming activity and an improvement of overall bone tissue quality.

Introduction: Various anti-osteoporotic agents are available for clinical use; however, there is still a need for drugs able to positively influence the coupling between bone formation and bone resorption to increase bone mass and bone strength. Strontium ranelate (PROTELOS), a new chemical entity containing stable strontium (Sr), was tested for its capacity to influence bone quality and quantity.