Effects of long-term alendronate treatment on postmenopausal osteoporosis bone material properties

Hassler, N.; Gamsjaeger, Sonja; Hofstetter, B.; Brozek, Wolfgang; Klaushofer, Klaus; Paschalis, Eleftherios P.

doi:10.1007/s00198-014-2929-5

Cited by 26 publications

(17 citation statements)

References 57 publications

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“…In addition to the control bone tissue, the Raman results for mineral/matrix, PG, and MMC were compared with previously published values from interstitial bone from postmenopausal patients that were on long term (10 years) ALN therapy (ALN-L), with no AFF incidence (Hassler et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

Presence of pyrophosphate in bone from an atypical femoral fracture site: A case report

et al. 2017

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Long-term antiresorptives use has been linked to atypical subtrochanteric and diaphyseal femoral fractures (AFF), the pathogenesis of which is still unknown. In the present case report we present the results of analysis of bone chips from a 74-year old female patient that had been on alendronate, ibandronate and denosumab treatment, and who sustained an atypical femoral fracture, by histology, quantitative backscattered electron imaging, and Raman spectroscopic analysis.The results indicate ongoing osteoclastic resorption, but also several abnormalities: 1) an altered arrangement of osteons; 2) impaired mineralization; 3) the presence of pyrophosphate, which might contribute to the impaired mineralization evident in the present case. Taken together, these changes may contribute to the focally reduced bone strength of this patient.

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Section: Methodsmentioning

confidence: 99%

Presence of pyrophosphate in bone from an atypical femoral fracture site: A case report

et al. 2017

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“…We are increasingly aware that there are some risks associated with treatment; there is limited evidence that longterm treatment with bisphosphonates may be associated with increased risk of some side effects. However, to date trials have been underpowered to detect these rare events and thus the risks of long-term treatments remain unclear, particularly given recent data to suggest that 10 years of alendronate therapy was associated with minimal, transient bone tissue composition changes [41], and a recent systematic review suggesting that patients with low bone density who remain at high risk of fracture should remain on therapy for long term given the persisting benefits of therapy and low risk of side effects [42]. Given the paucity of well-designed randomized controlled trials to substantiate the long-term benefits and risks of bisphosphonates and denosumab for osteoporosis in postmenopausal women, future tr ials are warranted.…”

Section: How To Agree Duration Of Therapymentioning

confidence: 96%

What is needed to advance the treatment of osteoporosis in the UK?

Dulay¹,

Dennison²

2015

International Journal of Clinical Rheumatology

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Osteoporosis is a condition associated with a very significant personal and public health burden. Worldwide, osteoporotic fractures account for 0.83% of the global burden of noncommunicable disease. Despite recent huge advances, adherence to osteoporosis therapy is often poor. There has been a recent growing awareness of rare, but potentially serious, side effects that appear more common in patients who taken therapy for several years. This perspective considers the very significant advances we have made in management of this common condition in recent years, and more particularly highlights the areas where we remain uncertain about how best to advise our patients -and how to ensure that those individuals at highest risk are identified and treated.

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“…46 Comparison of longterm effects on collagen properties in the biopsies from patients of the fracture intervention long-term (10 years) extension study gave evidence for similar collagen properties after 10 years compared with 5 years with alendronate. 47 In another study, zoledronic acid treatment had an influence on tissue maturation compared with placebo. 48 Mineral:matrix ratios, for instance, of few days old bone matrix was higher in the patients on active treatment compared with placebo.…”

Section: Effects On Collagen Propertiesmentioning

confidence: 98%

“…45 Apart from studying the effect of bone turnover reduction by considering larger bone area/volume for analysis of collagen properties, one can also consider bone of a specific tissue age, in particular young bone. [46][47][48] From the latter, one might obtain information on the state of maturation of the tissue and in turn on eventual changes in the kinetics of tissue maturation in treated versus untreated bone. Collagen cross-link ratios in newly formed tissue from treated patients were observed to be dependent on the type of bisphosphonate: alendronate or risedronate.…”

Section: Effects On Collagen Propertiesmentioning

confidence: 99%

“…46 This bone quality metric was also similar between patients who were on alendronate for either 5 or 10 years. 47 Effects on bone matrix mineralization The aforementioned collagen properties and the amount of mineral particles embedded in the collagenous matrix are important determinants of overall material elasticity, toughness and strength. The weight or volume fraction of mineral in the bone matrix is measured spatially resolved by methods such as microradiography, synchrotron mCT and quantitative backscattered electron microscopy typically obtained from the entire volume or cross-sectional area of bone biopsy samples.…”

Section: Effects On Bone Mineralmentioning

confidence: 99%

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Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects

et al. 2015

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It is well established that long-term antiresorptive use is effective in the reduction of fracture risk in high bone turnover osteoporosis. Nevertheless, during recent years, concerns emerged that longer bone turnover reduction might favor the occurrence of fatigue fractures. However, the underlying mechanisms for both beneficial and suspected adverse effects are not fully understood yet. There is some evidence that their effects on the bone material characteristics have an important role. In principle, the composition and nanostructure of bone material, for example, collagen cross-links and mineral content and crystallinity, is highly dependent on tissue age. Bone turnover determines the age distribution of the bone structural units (BSUs) present in bone, which in turn is decisive for its intrinsic material properties. It is noteworthy that the effects of bone turnover reduction on bone material were observed to be dependent on the duration of the antiresorptive therapy. During the first 2-3 years, significant decreases in the heterogeneity of material properties such as mineralization of the BSUs have been observed. In the long term (5-10 years), the mineralization pattern reverts towards normal heterogeneity and degree of mineralization, with no signs of hypermineralization in the bone matrix. Nevertheless, it has been hypothesized that the occurrence of fatigue fractures (such as atypical femoral fractures) might be linked to a reduced ability of microdamage repair under antiresorptive therapy. The present article examines results from clinical studies after antiresorptive, in particular long-term, therapy with the aforementioned potentially positive or negative effects on bone material.

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Effects of long-term alendronate treatment on postmenopausal osteoporosis bone material properties

Abstract: The data suggest that prolonged reduction in bone turnover during 10 years of therapy with ALN by itself is unlikely to be associated with adverse effects on bone material properties.

Cited by 26 publications

References 57 publications

Presence of pyrophosphate in bone from an atypical femoral fracture site: A case report

Presence of pyrophosphate in bone from an atypical femoral fracture site: A case report

What is needed to advance the treatment of osteoporosis in the UK?

Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects

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