Anabolic Therapy for Osteoporosis

Abstract

All currently available, approved therapies for osteoporosis inhibit bone resorption. By acting at this site in the bone remodeling cycle, estrogens, selective estrogen receptor modulators, calcitonin, and the bisphosphonates all have the capacity to increase bone mineral density and to reduce the risk of new fractures. There can be no doubt that these agents have had an enormous impact on our diagnostic and therapeutic approach to osteoporosis. Despite their great value, the antiresorptives are generally not associated with dramatic increases in bone mass, and their action to reduce fracture risk, although highly significant, is rarely more than 50% of the baseline risk. Another approach is anabolic therapy, in which bone formation is directly stimulated. In this review we will summarize the anabolic agents that have been studied and present a current view of their current standing. Fluoride, GH, insulin-like growth factor I, the statins, and PTH will be reviewed. Although still in development, approaches to combination therapy with antiresorptives and anabolic agents are also promising.

Osteopontin Negatively Regulates Parathyroid Hormone Receptor Signaling in Osteoblasts

“…One microgram of total RNA was treated with DNase I (Invitrogen) before reverse transcription. First-strand cDNA was synthesized using SuperScript II transcriptase and oligo(dT) [12][13][14][15][16][17][18] primers (Invitrogen). Quantitative real-time PCR analysis was carried out using an iCycler (Bio-Rad) and iQ5 data analyzing software.…”

“…Currently, no rational counter-modalities are available for osteosarcoma. Second, fractures in patients treated with PTH still occurs, although the rate is significantly reduced (13). This fact indicates that PTH alone is not enough to fully prevent fractures associated with osteoporosis (14,15).…”

Parathyroid Hormone-responsive Smad3-related Factor, Tmem119, Promotes Osteoblast Differentiation and Interacts with the Bone Morphogenetic Protein-Runx2 Pathway

“…However, many aspects of osteoblastic bone formation remain to be understood. Intermittent parathyroid hormone (PTH) 3 is one of the most potent anabolic agents; it stimulates de novo osteoblastic bone formation and is superior to bisphosphonates in the treatment of osteoporosis (1,2). The anabolic action of PTH is exerted partly through local growth factors and transcriptional regulators as well by as an anti-apoptotic action in osteoblasts (3,4).…”

“…1 Supported by a Kidney Foundation of Canada Biomedical Fellowship and a fellowship from the Research Institute of the McGill University Health Centre. 2 To whom correspondence should be addressed: Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. enhanced ␤-catenin levels at early times independently of endogenous TGF-␤.…”

Calcyclin, a Ca2+ Ion-binding Protein, Contributes to the Anabolic Effects of Simvastatin on Bone

“…Anti-resorptive agents stabilize the bone remodeling by reducing the number and/or the activity of osteoclasts, thereby reducing the risk of fracture without increments of true bone mass (4). In contrast, anabolic agents such as parathyroid hormone (PTH), 1 statin, and fluoride directly stimulate bone formation and increase bone mass (5,6). Recently, the Food and Drug Administration approved PTH as the first bone anabolic agent for severe osteoporosis.…”