Bisphosphonates Stimulate Formation of Osteoblast Precursors and Mineralized Nodules in Murine and Human Bone Marrow Cultures In Vitro and Promote Early Osteoblastogenesis in Young and Aged Mice In Vivo

Giuliani, Nicola; Pedrazzoni, M.; Negri, G.; Passeri, Giovanni; Impicciatore, M; Girasole, G.

doi:10.1016/s8756-3282(98)00033-7

Cited by 244 publications

(191 citation statements)

References 32 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: 91%

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: 91%

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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“…Recent in vitro studies suggest that bisphosphonates impact both bone resorption and bone formation [39][40][41][42]. It was reported that bisphosphonates inhibit osteoclastic activity and exert an anabolic effect on osteoblasts by altering osteoblast-specific gene expression and enhancing differentiation of human BMSCs [39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that bisphosphonates inhibit osteoclastic activity and exert an anabolic effect on osteoblasts by altering osteoblast-specific gene expression and enhancing differentiation of human BMSCs [39][40][41][42]. Bisphosphonates may also contribute to increasing the life span of osteoblasts through mechanisms that inhibit osteoblast apoptosis [43].…”

Section: Discussionmentioning

confidence: 99%

Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation

Pettway

Meganck

Koh

et al. 2008

Bone

107

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PTH (1-34) is the only FDA-approved anabolic agent for osteoporosis treatment in the U.S., but its mechanisms are not completely understood. This study investigated PTH effects on osteogenic cells at various stages of differentiation and proliferation using an engineered bone growth model in vivo. Ossicles were generated from bone marrow stromal cells (BMSCs) implanted in immunocompromised mice. Three weeks of PTH (40μg/kg/d) or vehicle treatment initiated 1 day, 1, 2, or 3wks after BMSC implantation resulted in an anabolic response in PTH-treated implants (via histomorphometry and microCT) in all treatment groups. A novel in vivo tracking strategy with luciferase tagged BMSCs and weekly bioluminescent imaging of ossicles revealed increased donor cell proliferation in PTH-treated ossicles. The greatest increase occurred during the first week, and the activity remained elevated in PTH-treated implants over time. Zoledronic acid (ZA) was combined with PTH to delineate interactive mechanisms of these bone active agents. Combining ZA with PTH treatment reduced the PTH-mediated increase in luciferase BMSC activity, serum osteocalcin, and serum tartrate resistant acid phosphotase-5b (TRAP-5b) but ZA did not reduce the PTH-induced increase in total bone. Since zoledronic acid reduced PTH-induced proliferation without reducing bone volume, these data suggests that combining PTH and bisphosphonate therapy warrants further investigation in the treatment of bone disorders.

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“…They directly enhance osteoblast proliferation and promote a differentiation of osteoprogenitor cells towards the osteoblastic pathway. 36,37 Bisphosphonates also prevent osteoblast apoptosis 38,39 and upregulate production of extracellular matrix proteins by osteoblasts. 35 These effects have been reported for different members of the bisphosphonate family, including zoledronic acid, pamidronate, neridronate, alendronate and risedronate.…”

Section: Discussionmentioning

confidence: 99%

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

Tauchmanovà

Simone

Musella

et al. 2005

Bone Marrow Transplant

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Bisphosphonates Stimulate Formation of Osteoblast Precursors and Mineralized Nodules in Murine and Human Bone Marrow Cultures In Vitro and Promote Early Osteoblastogenesis in Young and Aged Mice In Vivo

Cited by 244 publications

References 32 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

Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

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