Alendronate and raloxifene affect the osteoprotegerin/RANKL system in human osteoblast primary cultures from patients with osteoporosis and osteoarthritis

Giner, Mercè; Rios, Ma José; Montoya, Ma José; Vázquez, M.A.; Miranda, Cristina; Pérez‐Cano, Ramón

doi:10.1016/j.ejphar.2010.10.058

Cited by 20 publications

(17 citation statements)

References 43 publications

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“…These results are reflective of the work of others (Giner et al, 2011;Kimachi et al, 2011;Koch et al, 2012), who observed that aminobisphosphonates, including alendronate and zoledronate, posed a modulatory effect on RANKL activity in osteoblastic cells. Considering that in this model the effect of bisphosphonates on an osteocytic network is being assessed, the results may be significant in further demonstrating the biochemical effect of osteoporotic drugs, most notably so in a model of microinjury in bone.…”

Section: Discussionsupporting

confidence: 70%

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation

Mulcahy

Curtin

McCoy³

et al. 2015

eCM

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Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis.

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Section: Discussionsupporting

confidence: 70%

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation

Mulcahy

Curtin

McCoy³

et al. 2015

eCM

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“…The loss of MMP2 can result in defects in osteoblast growth and decreased BMD at the tissue level . More importantly, the RANKL/OPG system has been widely reported as a major signaling pathway that regulates bone resorption . The increased RANKL/OPG ratio in the vibrated cell group favors osteoclastogenesis and bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Administration duration influences the effects of low‐magnitude, high‐frequency vibration on ovariectomized rat bone

Qing

Xie

Liem

et al. 2015

Journal Orthopaedic Research

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Low-magnitude, high-frequency vibration (LMHFV) has been proposed as a non-drug anti-osteoporosis treatment. However, the influence of administration duration on its effect is seldom investigated. In this study, the effect of 16-week LMHFV (0.3 g, 30 Hz, 20 min/day) on the bone mineral densities (BMDs), bone mechanical properties, and cellular responses of osteoporotic and healthy rats was examined by in vivo peripheral quantitative computed tomography (pQCT), fracture tests, cell assays, and mRNA quantification. Forty-eight adult rats were equally assigned to sham surgery (SHM), sham surgery with LMHFV (SHMþV), ovariectomy (OVX), and ovariectomy with LMHFV (OVXþV) groups. At week 8, LMHFV ameliorated ovariectomy-induced deterioration of trabecular bone, with a significantly higher tibia trabecular BMD (þ11.2%) being noted in OVXþV rats (vs. OVX). However, this positive effect was not observed at later time points. Furthermore, 16 weeks of LMHFV caused significant reductions in the vertebral mean BMD (À13.0%), trabecular BMD (À15.7%), and maximum load (À21.5%) in OVXþV rats (vs. OVX). Osteoblasts derived from osteoporotic rat bone explants showed elevated BSP and OSX mRNA expression induced by LMHFV on day 1. However, no further positive effect on osteoblastic mRNA expression, alkaline phosphatase activity, or calcium deposition was observed with prolonged culture time. A higher ratio of RANKL/OPG induced by LMHFV suggests that osteoclastogenesis may be activated. Together, these results demonstrate that administration duration played an important role in the effect of LMHFV. Early exposure to LMHFV can positively modulate osteoporotic bone and osteoblasts; however, the beneficial effect seems not to persist over time. Osteoporotic fracture is a significant cause of morbidity and mortality in the elderly.1 As a mechanosensitive tissue, bone adapts its mass, microstructure, and strength in response to dynamic mechanical loading. Hence, people with osteoporosis are encouraged to exercise their musculoskeletal system, as bone mineral density (BMD) can be improved by moderate-to-high-intensity weight-bearing physical activity.2,3 However, few elderly individuals are able to undertake these exercises. One possible alternative modality is low-magnitude, high-frequency vibration (LMHFV), which is performed in a low-impact manner with the possibility of producing results similar to those of physical exercises.4,5 A precursory study in 2001 reported the powerful osteogenic potential of LMHFV, in which the hind limbs of ovine were subjected to mechanical vibration (30 Hz, 0.3 g) resulting in a 34% higher trabecular bone density in the proximal femur compared with that in the control.6 LMHFV has been proposed as a non-pharmacological approach for the prevention and treatment of osteoporosis in elderly postmenopausal women. 7-9Scientific research with respect to LMHFV has been prolific in the past decade. However, initial attempts to stimulate osteoporotic bone formation using this approach have not been uniformly...

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“…The OVX model (group III) displayed significant bone loss after 12 weeks as depicted by evident reduction in the bone mineral contents (BMCs) of Ca in the femur as compared with an age-matched sham group. However, OPG functions as a soluble decoy receptor to RANKL and competes with RANK for RANKL binding to inhibit OC recruitment, thereby controlling OB-OC activity balance [37][38][39]. Low estradiol is certainly one possible RANK receptor on hematopoietic OC precursor cells enhances OC recruitment and activation.…”

Section: Discussionmentioning

confidence: 99%

Histological study of the femur and the lumbar vertebrae in ovariectomized adult albino rats following administration of collagen hydrosylate

Moneim

Mahmoud

2013

The Egyptian Journal of Histology

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Alendronate and raloxifene affect the osteoprotegerin/RANKL system in human osteoblast primary cultures from patients with osteoporosis and osteoarthritis

Cited by 20 publications

References 43 publications

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation

Administration duration influences the effects of low‐magnitude, high‐frequency vibration on ovariectomized rat bone

Histological study of the femur and the lumbar vertebrae in ovariectomized adult albino rats following administration of collagen hydrosylate

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