Skeletal accumulation of bisphosphonates: implications for osteoporosis treatment

Allen, Matthew R.

doi:10.1517/17425255.4.11.1371

Cited by 39 publications

(31 citation statements)

References 46 publications

(3 reference statements)

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“…Interestingly, the number of empty lacunae in the submucosal bone significantly increased after long-term treatment, suggesting that this finding may be associated with the cumulative doses fixed in the alveolar bone. This fact is in agreement with previous clinical and experimental reports (Ruggiero et al 2009;Marx et al 2005;Allen 2008;Aguirre et al 2012), supporting the hypothesis that long-term exposure to high doses of aminobisphosphonates determines their accumulation in alveolar BMUs, inducing local changes and constituting a potential first step in the development of osteonecrosis of the jaw (Allen 2008;Hoff et al 2008;Daubiné et al 2007;Pozzi et al 2009). …”

Section: Discussionsupporting

confidence: 89%

Severe compromise of preosteoblasts in a surgical mouse model of bisphosphonate-associated osteonecrosis of the jaw

Córdova

Guilbaud

Amiaud

et al. 2016

Journal of Cranio-Maxillofacial Surgery

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Objectives: The effect of amino-bisphosphonates on osteoblastic lineage and its potential contribution to the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw (BONJ) remain controversial. We assessed the effects of zoledronic acid (ZOL) on bone and vascular cells of the alveolar socket using a mouse model of BONJ. Material and methods: Thirty-two mice were treated twice a week with either 100 mu g/kg of ZOL or saline for 12 weeks. The first left maxillary molar was extracted at the third week. Alveolar sockets were assessed at both 3 weeks (intermediate) and 9 weeks (long-term) after molar extraction by semi quantitative histomorphometry for empty lacunae, preosteoblasts (Osterix), osteoclasts (TRAP), and pericyte-like cells (CD146). Also, the bone microarchitecture was assessed by micro-CT. Results: Osteonecrotic-like lesions were observed in 21% of mice. Moreover, a decreased number of preosteoblasts contrasted with the increased number of osteoclasts at both time points. In addition, osteoclasts display multinucleation and detachment from the endosteal surface. Furthermore, the number of pericyte-like cells increased at the intermediate time point. The alveolar bone mass increased exclusively with long-term ZOL treatment. Conclusion: The severe imbalance between bone-forming cells and bone-resorbing cells shown in this study could contribute to the pathogenesis of BONJ

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Section: Discussionsupporting

confidence: 89%

Severe compromise of preosteoblasts in a surgical mouse model of bisphosphonate-associated osteonecrosis of the jaw

Córdova

Guilbaud

Amiaud

et al. 2016

Journal of Cranio-Maxillofacial Surgery

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“…Bisphosphonates are cost-effective treatment for management of osteoporosis and they reduce morbidity, disability, and mortality associated with fractures [1][2][3][4][5][6][7][8][9][10][11][12][13]. However, our observations suggest care must be taken when prescribing bisphosphonates for prolonged periods and doctors should be alerted by symptoms of thigh pain in patients taking them, because this may be a symptom of insufficiency changes in the femoral shaft.…”

Section: Discussionmentioning

confidence: 82%

“…In addition, chronic oversuppression of bone turnover by bisphosphonates may allow secondary mineralization to continue, producing hypermineralized bone that may be more brittle [2,13,18,46,59]. Other theories to explain this association have been proposed, including those relating bone brittleness caused by long-term alendronate therapy to trabecular bone collagen cross-linking and isomerization [3,55]. Others suggest it may be attributable to osteoclastic abnormalities or a variant form of osteoporosis [6,65].…”

Section: Introductionmentioning

confidence: 99%

Femoral Insufficiency Fractures Associated with Prolonged Bisphosphonate Therapy

Isaacs

Shidiak

Harris

et al. 2010

Clinical Orthopaedics &Amp; Related Research

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“…They reduce bone resorption and bone loss either through the inhibition of the protein prenylation or the accumulation of toxic metabolites [66]. Some bisphosphonates are more tolerated than others; specifically, the adverse effects of alendronate are relatively mild with some transient gastrointestinal tract problems and some serious but uncommon events (esophagitis, gastric/duodenal ulceration/bleeding) [67].…”

Section: Current Treatment Optionsmentioning

confidence: 99%

The Effects of Variation in Collagen D-Spacing on Compact Bone Viscoelasticity: A Finite Element Analysis

Mendoza¹

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The D-spacing that is characteristic of collagen and its structural arrangement was previously thought to be a constant value. Much research is revealing that it is actually a distribution of values in biological tissues. Recent ovine experimentation has also shown that the D-spacing distribution is significantly altered following estrogen depletion. While ewes contain some major biological differences between their human counterparts, they are an economical and robust large animal model for postmenopausal osteoporosis. So, the exploration of the possible implications that D-spacing has on the mechanical properties of the whole bone utilizing animal models and computational methods is warranted. Six Warhill ewes were used in this experiment and were either ovariectomized or underwent a sham surgery. The animals were sacrificed after 3 years and the radius and ulna bone were harvested for further analysis. Rectangular beams of compact bone tissue were machined from six different sectors in the whole bone and dynamic mechanical analysis tests were performed on the 24 specimens. The

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Skeletal accumulation of bisphosphonates: implications for osteoporosis treatment

Cited by 39 publications

References 46 publications

Severe compromise of preosteoblasts in a surgical mouse model of bisphosphonate-associated osteonecrosis of the jaw

Severe compromise of preosteoblasts in a surgical mouse model of bisphosphonate-associated osteonecrosis of the jaw

Femoral Insufficiency Fractures Associated with Prolonged Bisphosphonate Therapy

The Effects of Variation in Collagen D-Spacing on Compact Bone Viscoelasticity: A Finite Element Analysis

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