Spectroscopic markers of bone quality in alendronate-treated postmenopausal women

Boskey, Adele L.; Spevak, Lyudmila; Weinstein, Robert S.

doi:10.1007/s00198-008-0725-9

Cited by 121 publications

(103 citation statements)

References 39 publications

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“…Without a complex statistical analysis requiring larger numbers, we can only suggest that no treatment corrected any FTIR-determined material property parameters in oim/oim of either sex to WT values. The increased heterogeneity discussed may be beneficial, because increased heterogeneity has been correlated with reduced fracture risk in untreated osteoporotic humans [6,14,20]. The lack of change in collagen maturity, noted to be slightly elevated in untreated male and female oim/oim cortical and cancellous bone, merits comment.…”

Section: Discussionmentioning

confidence: 99%

“…The distribution (heterogeneity) of each parameter is calculated based on the full width at half maximum of the pixel histogram for spatial distribution in each individual image. Heterogeneity in adult human bone has been shown to decrease with bisphosphonate treatment [6,14,20]. These compositional parameters, taken together, provide an index of bone quality.…”

Section: Introductionmentioning

confidence: 99%

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Are Changes in Composition in Response to Treatment of a Mouse Model of Osteogenesis Imperfecta Sex-dependent?

Boskey

Marino

Spevak

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Osteogenesis imperfecta (OI) is a genetic disease characterized by skeletal fragility and deformity. There is extensive debate regarding treatment options in adults with OI. Antiresorptive treatment reduces the number of fractures in growing oim/oim mice, an animal model that reproducibly mimics the moderate-to-severe form of OI in humans. Effects of long-term treatments with antiresorptive agents, considered for treatment of older patients with OI with similar presentation (moderate-tosevere OI) are, to date, unknown. Questions/purposes Fourier transform infrared (FTIR) imaging, which produces a map of the spatial variation in chemical composition in thin sections of bone, was used to address the following questions: (1) do oim/oim mice show a sex dependence in compositional properties at 6.5 months of age; (2) is there a sex-dependent response to treatment with antiresorptive agents used in the treatment of OI in humans; and (3) are any compositional parameters in oim/oim mice corrected to wild-type (WT) values after treatment? Methods FTIR imaging data were collected from femurs from four to five mice per sex per genotype per treatment. Treatments were 24 weeks of saline, alendronate, or RANKFc; and 12 weeks of saline + 12 weeks RANK-Fc and 12 weeks of alendronate + RANK-Fc. FTIR imaging compositional parameters measured in cortical and cancellous bones were mineral-to-matrix ratio, carbonate-to-mineral ratio, crystal size/perfection, acid phosphate substitution, collagen maturity, and their respective distributions (heterogeneities). Because of the small sample size, nonparametric statistics (Mann-Whitney U-and Kruskal-Wallis tests with Bonferroni correction) were used to compare saline-treated male and female mice of different genotypes and treatment effects by sex and genotype, respectively. Statistical significance was defined as p \ 0.05.One or more of the authors (CLR) has received research funding from Amgen (Thousand Oaks, CA, USA) in partial support of this study in an amount less than USD 10,000. One or more of the authors (ALB) owns stock in Amgen (Thousand Oaks, CA) in an amount less than USD 10,000 and in Merck (Kenilworth, NJ, USA) in an amount less than USD 10,000. Results At 6.5 months, saline-treated male cortical oim/ oim bone had increased mineral-to-matrix ratio (p = 0.016), increased acid phosphate substitution (p = 0.032), and decreased carbonate-to-mineral ratio (p = 0.016) relative to WT. Cancellous bone in male oim/oim also had increased mineral-to-matrix ratio (p = 0.016) relative to male WT. Female oim/oim mouse bone composition for all cortical and cancellous bone parameters was comparable to WT (p [ 0.05). Only the female WT mice showed a response of mean compositional properties to treatment, increasing mineral-to-matrix after RANK-Fc treatment in cancellous bone (p = 0.036) compared with saline-treated mice. Male oim/oim increased mineral-to-matrix cortical and cancellous bone heterogeneity in response to all long-term treatments except for saline + RANK-Fc (p...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Are Changes in Composition in Response to Treatment of a Mouse Model of Osteogenesis Imperfecta Sex-dependent?

Boskey

Marino

Spevak

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…Using Fourier-transformed infrared spectroscopy (FTIR), Durchschlag and colleagues (30) showed that BP treatment prevented the maturation of collagen found in patients not treated with BPs and reduced collagen maturity in newly formed bone. Boskey and colleagues (31) reported no change in collagen maturity in women treated with alendronate. Donnelly and colleagues (32) showed similar mean values but a narrowed distribution of collagen maturity and enzymatic crosslinks in a small number of women with common proximal femoral fractures without features of atypia who had been treated with BPs for an average of 7 years.…”

Section: Insights Into the Pathogenesis Of Atypical Femoral Fracturesmentioning

confidence: 96%

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

988

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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“…(10,(58)(59)(60) Both short-term and long-term RIS administration resulted in mineral crystallites of decreased maturity/crystallinity compared to ALN, in general agreement with previously published reports showing that although RIS administration in postmenopausal women lowered this bone quality index compared to placebo, ALN did not. (12,13) Collagen cross-links are also important contributors to bone strength. (10,11,37,38) It should be noted that in cases for which bone strength and BMD exhibit divergent trends, the mineral maturity/crystallinity and collagen cross-links ratio correlate with the former rather than the latter.…”

Section: Discussionmentioning

confidence: 99%

“…(11) Spectroscopic analysis of biopsies from postmenopausal women who received either placebo or ALN (10 mg/d) for 3 years revealed no significant changes between the two groups in spectroscopic markers of bone quality (mineral/matrix ratio, crystallinity, carbonate/amide I ratio, and collagen maturity), except for a significant increase in cortical bone mineral content in the patients who were receiving ALN. (12) On the other hand, spectroscopic analysis of biopsies from postmenopausal women who received either placebo or RIS for 3 or 5 years showed that RIS arrested the tissue aging encountered in untreated osteoporosis. In particular, patients who received placebo exhibited increased mineral maturity/ crystallinity and collagen cross-link ratio after 3 and 5 years compared with baseline values, whereas patients who received RIS had no significant changes in either parameter at 3 or 5 years compared to baseline.…”

Section: Introductionmentioning

confidence: 99%

Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces

Hofstetter

Gamsjaeger

Phipps³

et al. 2012

Journal of Bone and Mineral Research

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We used Raman and Fourier transform infrared microspectroscopy (FTIRM) analysis to examine the intrinsic bone material properties at actively bone-forming trabecular surfaces in iliac crest biopsies from women with postmenopausal osteoporosis (PMO) who were treated with either alendronate (ALN) or risedronate (RIS). At eight study sites, women were identified who had postmenopausal osteoporosis (PMO), were at least 5 years postmenopause, and had been on long-term therapy (either 3-5 years or >5 years) with daily or weekly ALN or RIS. Following standard tetracycline labeling, biopsies were collected from 102 women (33 treated with ALN for 3-5 years , 35 with ALN for >5 years , 26 with RIS for 3-5 years , and 8 with RIS for >5 years ) and were analyzed at anatomical areas of similar tissue age in bone-forming areas (within the fluorescent double labels). The following outcomes were monitored and reported: mineral to matrix ratio (corresponding to ash weight), relative proteoglycan content (regulating mineralization commencement), mineral maturity (indicative of the mineral crystallite chemistry and stoichiometry, and having a direct bearing on crystallite shape and size), and the ratio of two of the major enzymatic collagen cross-links (pyridinoline/divalent). In RIS-5 there was a significant decrease in the relative proteoglycan content (À5.83% compared to ALN-5), while in both RIS-3 and RIS-5 there was significantly lower mineral maturity/ crystallinity (À6.78% and À13.68% versus ALN-3 and ALN-5, respectively), and pyridinoline/divalent collagen cross-link ratio (À23.09% and À41.85% versus ALN-3 and ALN-5, respectively). The results of the present study indicate that ALN and RIS exert differential effects on the intrinsic bone material properties at actively bone-forming trabecular surfaces. ß

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Spectroscopic markers of bone quality in alendronate-treated postmenopausal women

Cited by 121 publications

References 39 publications

Are Changes in Composition in Response to Treatment of a Mouse Model of Osteogenesis Imperfecta Sex-dependent?

Are Changes in Composition in Response to Treatment of a Mouse Model of Osteogenesis Imperfecta Sex-dependent?

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

Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces

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