Constant mineralization density distribution in cancellous human bone

Roschger, Paul; Gupta, Himadri S.; Berzlanovich, Andrea; Ittner, G.; Dempster, David W.; Fratzl, Peter; Cosman, Felicia; Parisien, May; Lindsay, Robert; Nieves, Jeri W.; Klaushofer, Klaus

doi:10.1016/s8756-3282(02)00973-0

Cited by 243 publications

(272 citation statements)

References 37 publications

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“…BMDD is a measure of the degree and heterogeneity of mineralization in bone tissue. (33)(34)(35) In the healthy adult population, BMDD of cancellous bone shows only minor variations with age, gender, ethnicity, and skeletal site, (36) indicating that the normal BMDD corresponds to a biologic and mechanical optimum. Therefore, even small deviations from the normal BMDD may have biologic meaning.…”

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

989

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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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

989

679

View full text Add to dashboard Cite

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“…Five variables were obtained for statistical comparison of the BMDD curves (28,29) : Ca Mean , the weighted mean calcium concentration of the bone area; Ca Peak , the mode calcium concentration (the peak position of the histogram), which indicates the most frequently occurring calcium concentration of the studied bone area; Ca Width , the full width at half maximum of the distribution, describing the variation in mineralization density; Ca Low , the percentage of mineralized bone with a calcium concentration less than the 5th percentile of the reference BMDD (less than 17.68 weight percent calcium), which approximates the amount of bone area undergoing primary mineralization; and Ca High , the portion of bone areas with a calcium concentration higher than the 95th percentile of the reference BMDD (higher than 25.30 weight percent calcium), which is predominantly interstitial bone. (28,29) The reference BMDD data were obtained from trabecular bone of a cohort of healthy individuals (n ¼ 52) from different skeletal sites (ie, transiliac bone, vertebrae, femoral neck and head, and patella). This cohort comprised adult individuals (aged 25 to 90 years) of different ethnicity (African Americans and white Americans) and gender.…”

Section: Patients and Biopsiesmentioning

confidence: 99%

“…Since none of these biologic factors was associated with significant differences in the BMDD, such a general reference trabecular BMDD for adults including all the biologic factors could be established. (29) Statistical analysis…”

Section: Patients and Biopsiesmentioning

confidence: 99%

“…BMDD variables of the study groups (priorALN or priorRIS) versus normal reference BMDD data (29) (cortical BMDD reference data were not available for comparison); (3) paired t tests were used for analysis of the changes from baseline within each study group separately (priorALN or priorRIS; for information on the teriparatide effects in one study group independent of the other); and (4) two-way repeated measures ANOVA was used for analyzing whether teriparatide had differential effects in the two study groups (priorALN versus priorRIS). Two-way repeated measures ANOVA tests three hypotheses: (1) There is no significant effect owing to the factor prior bisphosphonate treatment, (2) there is no significant effect owing to the factor 1 year of teriparatide treatment, and (3) there is no interaction between the factor prior bisphosphonate and the factor 1 year of teriparatide, indicating that the changes from baseline in one prior bisphosphonate group are not significantly different from those in the other prior bisphosphonate group.…”

Section: Patients and Biopsiesmentioning

confidence: 99%

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Effects of 1 year of daily teriparatide treatment on iliacal bone mineralization density distribution (BMDD) in postmenopausal osteoporotic women previously treated with alendronate or risedronate

Misof

Paschalis

Blouin

et al. 2010

Journal of Bone and Mineral Research

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Anabolic treatment with teriparatide of postmenopausal osteoporotic patients previously treated with bisphosphonates is a new therapeutic approach. However, its effects on the bone mineralization density distribution (BMDD) are unknown. We studied paired transiliac bone biopsy samples taken before and after 1 year of treatment with recombinant human parathyroid hormone peptide 1-34 (teriparatide) from 16 osteoporotic women treated with either alendronate (priorALN) or risedronate (priorRIS) for at least 2 years and subsequently treated for 12 months with teriparatide. Cancellous (Cn.) and cortical (Ct.) BMDD values were measured using quantitative backscattered electron imaging. At baseline, BMDD values of priorALN and priorRIS women were similar and within the normal range. One year of teriparatide treatment caused significant effects on the BMDD. Analyzing changes from baseline for each bisphosphonate group separately, priorALN patients revealed increases in the portion of low mineralized bone areas (Cn.Ca Low þ25.9%, Ct.Ca Low þ62.0%, both p < .05) and Ct. heterogeneity of mineralization (Ct.Ca Width þ22.8%, p < .001). PriorRIS patients showed increased mineralization heterogeneity (Cn.Ca Width þ14.8%, p < .05, and Ct.Ca Width þ15.8%, p < .001). Analysis of the influence of the prior bisphosphonate treatment showed that the BMDD response to 1 year of teriparatide treatment did not depend on the type of prior bisphosphonate. In consequence, priorALN and priorRIS groups were combined. The pooled groups revealed increased Cn.Ca Width and Ct.Ca Width (þ10.7%, p < .01, and þ19.6%, p < .001, respectively) as well as increased Cn.Ca Low and Ct.Ca Low (þ18.2%, p < .05, and þ36.6%, p < .01, respectively). In summary, our findings indicate a significant effect of teriparatide on BMDD when administered subsequent to a bisphosphonate in agreement with teriparatide's anabolic action. ß

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“…16 Parameters obtained from BMDD include the average and mode Ca content and the full-width at half-maximum of the BMDD peak, which is a measure of the heterogeneity of mineralization. Deviations from normal calcium distributions have been reported to date in: osteomalacia, 17 osteoporosis 18 and idiopathic osteoporosis 19 (peak shifted to the left of normal), classical and new forms of osteogenesis imperfecta 16,20 (peak shifted to the right of normal) and treatment with some but not all bisphosphonates examined by this technique. 18,21,22 Variation in phosphate distribution is visualized by both Fourier transform infrared microscopic imaging (FTIRI) 23 and Raman microscopy and imaging (Raman).…”

Section: Bone Mineralmentioning

confidence: 88%

Bone composition: relationship to bone fragility and anti-osteoporotic drug effects

Boskey¹

2015

BoneKEy Reports

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Constant mineralization density distribution in cancellous human bone

Cited by 243 publications

References 37 publications

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

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

Effects of 1 year of daily teriparatide treatment on iliacal bone mineralization density distribution (BMDD) in postmenopausal osteoporotic women previously treated with alendronate or risedronate

Bone composition: relationship to bone fragility and anti-osteoporotic drug effects

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