Microcrack Frequency and Bone Remodeling in Postmenopausal Osteoporotic Women on Long-Term Bisphosphonates: A Bone Biopsy Study

Chapurlat, Roland; Arlot, M.; Burt‐Pichat, Brigitte; Chavassieux, Pascale; Roux, Jean-Paul; Portero-Muzy, Nathalie; Delmas, Pierre D.

doi:10.1359/jbmr.070609

Cited by 142 publications

(108 citation statements)

References 49 publications

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“…Another explanation might be that pressure at the joints caused necrosis of the local bone tissues, compressing the vessels inside the medullary cavity, thus resulting in ischemia and necrosis of local tissues, followed by the structural damage to the trabecular bone. This mechanism has been reported for intraosteal pseudocyst formation in OA subchondral bone (Nehme et al, 2003;Chapurlat et al, 2007), which is characterized by decreases in BVF, Tb.N, Tb.Th, and vBMD. As the vBMD of the subchondral bone is reduced, the structure becomes damaged, and so a reduction in its mechanical properties is inevitable.…”

Section: Discussionsupporting

confidence: 65%

3-D Structural Changes in Subchondral Bone and the Effect of Bisphosphonate Intervention in Early Osteoarthritis

2016

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SUMMARY:This study aims to observe the 3-D structural changes in subchondral bone and the effects of bisphosphonate intervention in the early unsteady stage of the knee joint. Sixty healthy male New Zealand white rabbits were divided into the model group (n= 24), the bisphosphonate (Bis) group (n= 24), and the control group (n= 12). The rabbits' right knees were used to evaluate the structural changes. The Bis group received subcutaneous injections of bisphosphonate, while the model and control groups received subcutaneous injections of isotonic saline solution. After surgical preparation, the knee joint was dissected for Micro-CT examination, and the Micro-CT results were compared using ANOVA. In the fourth postoperative week, the bone volume fraction (BVF), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the model group were significantly lower than those of the control group (P<0.01). There was no significant difference between the Bis and control groups. In the twelfth postoperative week, BVF, Tb.Th, and Tb.N of the model group were significantly higher than those of the control and Bis groups (P <0.05). Similarly, bone mineral density was higher in the model group (P <0.01), while the trabecular spacing was significantly lower (P <0.05). In the early unsteady stage of the knee joint, the subchondral bone had markedly decreased, while obvious bone formation was visible in the late stage. Bisphosphonates could protect the subchondral bone structure by inhibiting bone absorption.

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Section: Discussionsupporting

confidence: 65%

3-D Structural Changes in Subchondral Bone and the Effect of Bisphosphonate Intervention in Early Osteoarthritis

2016

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“…However, Stepan et al were able to show definitively that microcrack accumulation is associated with age, low BMD, and prevalent fractures. Others, however, have not found an association between BP treatment and damage accumulation in the iliac crest [68]. However, this study used an aged, incompletely characterized control sample from the dissecting room.…”

Section: Bps and Microdamage -What We Don't Know (Table 2)mentioning

confidence: 98%

Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

Allen

Burr

2011

Bone

195

159

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This is the author's manuscript of the article published in final edited form as: Allen M. R., Burr D.B. (2011 A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractThe bisphosphonates (BPs) have been useful tools in our understanding of the role that bone remodeling plays in skeletal health. The purpose of this paper is to outline what we know, and what is still unknown, about the role that BPs play in modulating bone turnover, how this affects microdamage accumulation, and ultimately what the effects of these changes elicited by BPs are to the structural and the material biomechanical properties of the skeleton. We know thatBPs suppress remodeling site-specifically, probably do not have a direct effect on formation, and that the individual BPs vary with respect to speed of onset, duration of effect and magnitude of suppression. However, we do not know if these differences are meaningful in a clinical sense, how much remodeling is sufficient, the optimal duration of treatment, or how long it takes to restore remodeling to pre-treatment levels. We also know that suppression is intimately tied to microdamage accumulation, which is also site-specific, that BPs impair targeted repair of damage, and that they can reduce the energy absorption capacity of bone at the tissue level.However, the BPs are clearly effective at preventing fracture, and generally increase bone mineral density and whole bone strength, so we do not know whether these changes in damage accumulation and repair, or the mechanical effects at the tissue level, are clinically meaningful.The mechanical effects of BPs to the fatigue life of bone, or BP effects on bone subject to an impact, are entirely unknown. This paper reviews the literature on these topics, and identifies gaps in knowledge that can be addressed with further research.

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“…(50) A second study did not find an association between BP treatment and damage accumulation in the iliac crest. (51) Neither study evaluated samples from the femoral cortex, and because the accumulation of microdamage is site-specific, it is unknown whether damage accumulates in the cortex of the femoral diaphysis.…”

Section: Insights Into the Pathogenesis Of Atypical Femoral Fracturesmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

998

679

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Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. ß

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Microcrack Frequency and Bone Remodeling in Postmenopausal Osteoporotic Women on Long-Term Bisphosphonates: A Bone Biopsy Study

Cited by 142 publications

References 49 publications

3-D Structural Changes in Subchondral Bone and the Effect of Bisphosphonate Intervention in Early Osteoarthritis

3-D Structural Changes in Subchondral Bone and the Effect of Bisphosphonate Intervention in Early Osteoarthritis

Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

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