Bisphosphonates Pamidronate and Zoledronic Acid Stimulate Osteoprotegerin Production by Primary Human Osteoblasts

Viereck, Volker; Emons, Günter; Lauck, Vanessa; Frosch, Karl‐Heinz; Blaschke, Sabine; Gründker, Carsten; Hofbauer, Lorenz C.

doi:10.1006/bbrc.2002.6510

Cited by 276 publications

(224 citation statements)

References 25 publications

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“…Overall, treatment resulted in an increase in this marker of bone formation in approximately 16.7% of women. This finding was unexpected: despite reports that bisphosphonates may stimulate osteoblast formation, (29,30) there is no histomorphometric evidence of an increase in bone formation with treatment (31) and in general bisphosphonates are thought to be antiresorptive and not anabolic. (32) Other studies, similar to the present one, are needed to support or refute this finding.…”

Section: Discussionmentioning

confidence: 92%

The potential value of monitoring bone turnover markers among women on alendronate

Bell

Hayen

Irwig

et al. 2011

Journal of Bone and Mineral Research

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Biochemical markers of bone turnover have been proposed to monitor the response to bisphosphonate therapy for osteoporosis, but this requires true between-person differences in the response to therapy. Using mixed models we analyzed three annual measurements of two markers (bone alkaline phosphatase [BAP] and cross-linked N-telopeptide of type I collagen [NTX]) from the Fracture Intervention Trial. We compared marker variation among women allocated to alendronate with that among women allocated to placebo to estimate how much variation was due to true between-person differences in response to treatment, and how much was due to random withinperson fluctuations unrelated to treatment. For both markers we found that the mean effect of treatment differed by the baseline level of the marker. After allowing for this and other effects, we found large true between-person differences in response to treatment for both markers, with a coefficient of variation (CV) for NTX of 25.1% and for BAP of 21.2%. However, random within-person fluctuation was even larger, with a CV for change in NTX of 42.5% and for change in BAP of 25.8%. Although repeated measurements have the potential to reduce within person variability, even triplicate baseline marker measurements resulted in an averaged value that was only within 31% of the true value with 95% certainty. In summary, although bone turnover markers appear promising for monitoring between-person differences in response to treatment, their use in clinical practice is currently limited by large random within-person variation. ß

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Section: Discussionmentioning

confidence: 92%

The potential value of monitoring bone turnover markers among women on alendronate

Bell

Hayen

Irwig

et al. 2011

Journal of Bone and Mineral Research

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“…Moreover, it was recently reported that ZA exhibits direct effects on osteoblast, altering expression of RANKL and OPG in vitro. 24,25 These effects might also affect bone remodeling and potentially alter tumor growth in vivo. For example, OPG has been shown to inhibit TRAIL-induced apoptosis of CaP cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms

Quinn

Brown

Zhang

et al. 2005

Prostate Cancer Prostatic Dis

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Zoledronic acid (ZA) has been shown to inhibit prostate tumor growth in vitro and have beneficial effects in patients with advanced prostate cancer (CaP). The aim of this study was to determine whether ZA exhibits direct anti-tumor effects on CaP cells in vivo. To distinguish the effects of inhibition of osteolysis and direct antitumor activity of ZA in vivo, we compared the results of treatment with ZA and osteoprotegerin (Fc-OPG), which inhibits osteolysis, but without significant direct anti-tumor effects. In vitro Fc-OPG had no significant effects on C4-2 proliferation, whereas ZA decreased proliferation. However, both agents decreased tumor growth in bone. Moreover, both increased bone volume and prevented the overall decreases in BMD associated with growth of C4-2 cells in bone. Our study provides novel and significant observations that the in vivo effects of ZA are consistent with indirect effects mediated by osteoclasts.

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“…In addition, there is evidence suggesting that some bisphosphonates also may prevent osteocyte and osteoblast apoptosis [ 171. Bisphosphonates may also induce osteoblast proliferation and differentiation and stimulate osteoprotegerin (OPG) production [6,9,27]. Furthermore, bisphosphonates may also inhibit migration and promote apoptosis of inflammatory cells, primarily of the monocyte lineage [4,5,12,13,19,24].…”

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confidence: 99%

Systemic and local ibandronate enhance screw fixation

Skoglund

Holmertz

Aspenberg

2004

Journal Orthopaedic Research

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The trauma involved with inserting implants into bone leads to an activation of the inflammatory response and an activation of osteoclasts. In addition, apoptosis of osteocytes in the surrounding area has been implicated in further activation of osteoclasts. If the balance between resorption and bone formation shortly after implantation favours resorption, an impairment of early fixation might ensue.Because bisphosphonates inhibit resorption, this study analyses whether they can improve early fixation. Stainless steel screws (M 1.7) were inserted into the tibiae of 76 male Sprague-Dawley rats. Daily subcutaneous injections of ibandronate (3 pg) or saline were given to 20 rats. The remaining rats received ibandronate or saline directly applied into the drill hole before the screw was inserted. Tibiae were harvested at 14 days. Mechanical tests were performed on 50 tibiae. Systemically treated tibiae were tested for pull-out strength alone. Locally treated tibiae were tested for either pull-out or torque resistance. The remaining 18 tibiae were prepared for histology.Systemic ibandronate increased the pull-out force at failure by 30% (p = 0.04). Local treatment increased the force at failure by 15% (p = 0.02) and stiffness by 28% (p = 0.01). In the removal torque measurements, local ibandronate increased the torquemoment at failure by 60% (p = 0.04), and the maximum friction moment by 51% (p = 0.04). Energy for turning the screw 1/4 revolution was increased by 68% (p = 0.02).These results demonstrate that early remodeling events plays an important role in screw fixation, and that systemic or local bisphosphonate treatment could be an effective pharmacological path to improve early implant fixation.

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Bisphosphonates Pamidronate and Zoledronic Acid Stimulate Osteoprotegerin Production by Primary Human Osteoblasts

Cited by 276 publications

References 25 publications

The potential value of monitoring bone turnover markers among women on alendronate

The potential value of monitoring bone turnover markers among women on alendronate

Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms

Systemic and local ibandronate enhance screw fixation

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