Bone Material Properties in Trabecular Bone From Human Iliac Crest Biopsies After 3- and 5-Year Treatment With Risedronate

Durchschlag, Erich; Paschalis, Eleftherios P.; Zoehrer, R.; Roschger, Paul; Fratzl, Peter; Recker, Robert R.; Phipps, Roger J.; Klaushofer, Klaus

doi:10.1359/jbmr.060701

Cited by 115 publications

(70 citation statements)

References 57 publications

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“…Although it was reported that there was an age-related increases in mineral crystallinity and that risedronate prevented this change in post-menopausal women [13], we did not detect difference in the crystal size between the aged OVX animals and those of age-match sham animals. Bisphosphonate treatments also did not seem to alter the crystal size.…”

Section: Discussioncontrasting

confidence: 92%

“…Postmenopausal women were treated with oral risedronate or placebo for 5 years, and the average degree of bone mineralization, estimated from iliac crest biopsies, increased by 4.2% after 3 years of treatment, which was sustained for another 2 years [27]. Risedronate also prevented the age-associated and estrogen deficiency-related elevation in mineral maturity/crystallinity and collagen cross-link ratios [13]. In a study on human calcanei, Follet et al [4] found that the degree of bone mineralization is a determinant of bone strength after adjustment for bone volume and other bone microarchitecture parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Apart from affecting bone mineral distribution, bisphosphonates have non-hydrolysable P-C-P bonds with high affinities for the hydroxyapatite crystals (mineral); moreover, they have been reported to regulate crystal growth and dissolution [12]. In another study of osteoporotic women treated with either risedronate or placebo for three years, age-related increases in both mineral crystallinity and collagen cross-link ratios were reported, while risedronate prevented these changes [13]. Prevention of the age-related growth in crystallinity may be one of the mechanisms for bisphosphonates' anti-resorptive effects.…”

Section: Introductionmentioning

confidence: 99%

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The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

Yao

Cheng

Koester

et al. 2007

Bone

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The treatment of osteoporotic women with bisphosphonates significantly reduces the incidence of bone fractures to a degree greater than can be explained by an increase in bone mineral density. In this Study, 18 month Fischer 344 rats were ovariectomized and treated with a single dose of risedronate (intravenous, iv, 500μg), zoledronic acid (iv, 100μg) or continuous raloxifene (2mg/ kg, po., 3x/wk). High resolution microCT was used to measure lumbar vertebral bone microarchitecture, the degree of bone mineralization (DBM) and the distribution of mineral. Small angle x-ray scattering was used to investigate mineral crystallinity. We found prolonged estrogen deficiency, reduced trabecular bone volume, and increased micro architecture bone compression strength. lowered the degree of mineralization. Treatment with resorptive agents (bisphosphonates > raloxifene) prevented the loss of mineralization, trabecular bone volume and bone compression strength. Crystal size was not changed with OVX or with anti-resorptive treatments. In conclusion, in the aged estrogen deficient rat model, single intravenous doses of two bisphosphonates were effective in maintaining the compressive bone strength for 180 days by reducing bone turnover, and maintaining the DBM to a greater degree than with raloxifene.

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Section: Discussioncontrasting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

Yao

Cheng

Koester

et al. 2007

Bone

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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.…”

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

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999

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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“…This appeared to result from effects on active bone-forming areas. (13) The purpose of the present study was to investigate whether ALN and RIS exert different effects on bone material properties (mineral/matrix, mineral maturity/crystallinity, relative proteoglycan content, and pyridinoline [pyr]/divalent collagen crosslink ratio) during bone formation. To do this, iliac crest biopsies from patients who received either ALN or RIS were analyzed by Raman and Fourier transform infrared microspectroscopy (FTIRM).…”

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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Bone Material Properties in Trabecular Bone From Human Iliac Crest Biopsies After 3- and 5-Year Treatment With Risedronate

Cited by 115 publications

References 57 publications

The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

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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