Impact of Treatments for Postmenopausal Osteoporosis (Bisphosphonates, Parathyroid Hormone, Strontium Ranelate, and Denosumab) on Bone Quality: A Systematic Review
ABSTRACT The objective of this systematic review was to examine the influence of treatments for postmenopausal osteoporosis (parathyroid hormone [PTH], bisphosphonates, strontium ranelate, and denosumab) on bone quality and discuss the clinical implications. Most bone-quality data for PTH is from teriparatide. Teriparatide results in a rapid increase in bone-formation markers, followed by increases in bone-resorption markers, opening an "anabolic window," a period of time when PTH is maximally anabolic. Teriparatide reverses the structural damage seen in osteoporosis and restores the structure of trabecular bone. It has a positive effect on cortical bone, and any early increases in cortical porosity appear to be offset by increases in cortical thickness and diameter. Bisphosphonates are antiresorptive agents which reduce bone turnover, improve trabecular microarchitecture, and mineralization. Concerns have been raised that the prolonged antiresorptive action of bisphosphonates may lead to failure to repair microdamage, resulting in microcracks and atypical fragility. Strontium ranelate is thought to have a mixed mode of action, increasing bone formation and decreasing bone resorption. Strontium ranelate improves cortical thickness, trabecular number, and connectivity, with no change in cortical porosity. Denosumab exerts rapid, marked, and sustained effects on bone resorption, resulting in falls in the markers of bone turnover. Evidence from bone-quality studies suggests that treatment-naive women, aged 60-65 years, with very low BMD T scores may benefit from PTH as primary therapy to improve bone substrate and build bone. Post-PTH treatment with bisphosphonates will maintain improvements in bone quality and reduce the risk of fracture.
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ABSTRACT: During the past 2 decades, many interventions were proven effective in the management of postmenopausal osteoporosis. The objective of an anti-osteoporosis treatment is to reduce fracture rates, ideally at all skeletal sites (i.e. spine, hip, and other non-spine). The armamentarium against osteoporosis includes anti-resorptive agents (i.e. bisphosphonates, selective estrogen receptor modulators and denosumab), bone-forming agents (i.e. peptides from the parathyroid hormone family) and one agent with a dual mechanism of action (i.e. strontium ranelate). All these medications combine anti-fracture efficacy with a reasonable benefit/risk profile. However, the choice of a particular chemical entity, in one individual patient is based on the knowledge and expertise of the physician. Prioritization of drugs should be based on the individual profile of the patient, the severity of osteoporosis and the specific contraindications, warnings and precautions of use of the various available medications.Best Practice & Research: Clinical Endocrinology & Metabolism 12/2014; DOI:10.1016/j.beem.2014.09.003 · 4.91 Impact Factor
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ABSTRACT: Quantitative ultrasound assessment of the cortical compartment of the femur neck (FN) is investigated with the goal of achieving enhanced fracture risk prediction. Measurements at the FN are influenced by bone size, shape and material properties. The work described here was aimed at determining which FN material properties have a significant impact on ultrasound propagation around 0.5 MHz and assessing the relevancy of different models. A methodology for the modeling of ultrasound propagation in the FN, with a focus on the modeling of bone elastic properties based on scanning acoustic microscopy data, is introduced. It is found that the first-arriving ultrasound signal measured in through-transmission at the FN is not influenced by trabecular bone properties or by the heterogeneities of the cortical bone mineralized matrix. In contrast, the signal is sensitive to variations in cortical porosity, which can, to a certain extent, be accounted for by effective properties calculated with the Mori-Tanaka method.Ultrasound in medicine & biology 01/2014; DOI:10.1016/j.ultrasmedbio.2013.11.010 · 2.10 Impact Factor
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ABSTRACT: Clinically significant serum parathyroid hormone (PTH) variations have been reported in multiple myeloma (MM) patients treated with proteasome inhibitors. To elucidate the association between serum PTH variations and proteasome inhibition in MM, the effect of PTH and PTHR1 ligands on the proteasome inhibitors bortezomib and carfilzomib in vitro and in vivo was determined. The MM cell lines ARP1, OC1 and 5TGM1 expressed mRNA and protein encoding PTH receptor 1 (PTHR1). Treatment of 5TGM1 cells with either PTH(1–34), bortezomib or carfilzomib alone dose-dependently inhibited 5TGM1 cell proliferation. However, treatment with the potent PTHR1 antagonist [TYR34]PTH(7–34) (PTH(7–34)) had no significant effect on myeloma cell proliferation and cell viability. In contrast, when used in combination with bortezomib or carfilzomib, PTH(7–34) treatment signif-icantly reduced the bortezomib or carfilzomib-associated decrease in cell proliferation. Treatment of the C57BL/ KaLwRij mouse myeloma model with either bortezomib or carfilzomib provided a significantly prolonged survival benefit compared to controls (p = 0.04; p = 0.01 respectfully). This potent anti-myeloma effect was completely abrogated by concomitant treatment with PTH(7–34). These results suggest an important role of the PTHR1 in the anti-myeloma effect of proteosome inhibition.Bone 12/2013; · 4.46 Impact Factor