This article appears in the following Rheumatology issue: Improvement of bone microarchitecture: the foundation for a better protection against osteoporotic fractures [View the issue table of contents]
Reviews |
Strontium ranelate improves bone microarchitecture in osteoporosis
1Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands
Correspondence to: Neveen A. T. Hamdy, Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. E-mail: n.a.t.hamdy{at}lumc.nl
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Abstract |
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In osteoporosis, disruption of bone remodelling leads to bone loss, microarchitectural damage and increased fracture risk, and the goal of any treatment for osteoporosis is to decrease this fracture risk. Available anti-resorptive and anabolic agents effectively achieve this goal by either suppressing or stimulating the activation frequency of bone remodelling units, and by improving the biomechanical properties of bone by a number of different mechanisms. Strontium ranelate represents a novel approach in the management of osteoporosis with proven anti-fracture efficacy. Two putative mechanisms have been proposed for the unique dual mode of action of strontium ranelate, rebalancing bone turnover in favour of bone formation: activation of the calcium- or other cation-sensing receptor, and increase in the expression of osteoprotegerin (OPG), coupled with a decrease in RANK ligand expression by the osteoblasts. In addition to these cellular changes, micro-CT analysis of bone biopsies from strontium ranelate-treated patients demonstrate improvement in intrinsic bone tissue quality as evidenced by increased trabecular number, decreased trabecular separation, lower structure model index and increased cortical thickness, associated with a shift in trabecular structure from rod-to plate-like configuration compared with controls. This review examines the evidence for the ability of strontium ranelate to improve bone microarchitecture in osteoporosis and explores the cellular and microstructural changes by which its anti-fracture efficacy may be achieved. No attempt is made at comparing the effects of strontium ranelate on bone microarchitecture with that of other anti-resorptive or anabolic osteoporosis agents.
KEY WORDS: Bone mineral density, Bone quality, Bone strength, Bone biopsy, Bone histomorphometry, micro-CT analysis, Dual mode of action, Calcium-sensing receptor, RANK/RANKL/OPG pathway
Submitted 4 February 2009;
revised version accepted 31 July 2009.
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