The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: A randomized study comparing intermittent treatment and an ADFR regime

Steiniche, Torben; Hasling, C; Charles, Peder; Eriksen, Erik Fink; Melsen, F.; Mosekilde, Leif

doi:10.1016/8756-3282(91)90038-k

Cited by 56 publications

(31 citation statements)

References 37 publications

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“…Bisphosphonates are compounds that significantly reduce the activation frequency for bone remodeling. Histologically, bisphosphonates reduce resorption depth and reduce activation frequency (17–20) . Depending on dosage, activation frequency with the newer generation bisphosphonates can be reduced as much as 93%, but the effect can be titrated by lower doses and shorter treatment periods (20–23) .…”

Section: Discussionmentioning

confidence: 99%

Suppressed Bone Turnover by Bisphosphonates Increases Microdamage Accumulation and Reduces Some Biomechanical Properties in Dog Rib

Mashiba

Hirano

Turner

et al. 2000

Journal of Bone and Mineral Research

629

314

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It has been hypothesized that suppression of bone remodeling allows microdamage to accumulate, leading to increased bone fragility. This study evaluated the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties of cortical bone in the dog rib. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group (CNT) was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with risedronate (RIS) at a dose of 0.5 mg/kg per day or alendronate (ALN) at 1.0 mg/kg per day orally. After sacrifice, the right ninth rib was assigned to cortical histomorphometry or microdamage analysis. The left ninth rib was tested to failure in three-point bending. Total cross-sectional bone area was significantly increased in both RIS and ALN compared with CNT, whereas cortical area did not differ significantly among groups. One-year treatment with RIS or ALN significantly suppressed intracortical remodeling (RIS, 53%; ALN, 68%) without impairment of mineralization and significantly increased microdamage accumulation in both RIS (155%) and ALN (322%) compared with CNT. Although bone strength and stiffness were not significantly affected by the treatments, bone toughness declined significantly in ALN (20%). Regression analysis showed a significant nonlinear relationship between suppressed intracortical bone remodeling and microdamage accumulation as well as a significant linear relationship between microdamage accumulation and reduced toughness. This study showed that suppression of bone turnover by high doses of bisphosphonates is associated with microdamage accumulation and reduced some mechanical properties of bone. (J Bone Miner Res 2000;15:613-620)

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Section: Discussionmentioning

confidence: 99%

Suppressed Bone Turnover by Bisphosphonates Increases Microdamage Accumulation and Reduces Some Biomechanical Properties in Dog Rib

Mashiba

Hirano

Turner

et al. 2000

Journal of Bone and Mineral Research

629

314

View full text Add to dashboard Cite

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“…Sixteen were [18][19][20][21][22][23][24][25], lack of randomization (7 trials) [26][27][28][29][30][31][32] and duration of less than 1 year (1 trial) [33]. Table 2 presents the characteristics of the 13 studies, including a total of 1267 women, that met the inclusion criteria.…”

Section: Trial Characteristicsmentioning

confidence: 99%

A Meta-analysis of Etidronate for the Treatment of Postmenopausal Osteoporosis

Cranney

Guyatt

Krolicki

et al. 2001

Osteoporosis International

118

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The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1-3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures.

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“…Bisphosphonates significantly reduce activation frequency and as a consequence, inhibit bone formation, thereby reducing the amount of bone formed . Thus, in many animal models the lack of bone formation makes it difficult to study the effects of bisphosphonates on bone matrix maturation.…”

Section: Discussionmentioning

confidence: 99%

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

et al. 2020

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To test how osteoporosis drugs affect bone matrix maturation during cortical bone remodeling, 72 pregnant rats were switched from a 0.4% to a 0.01% calcium diet at parturition for a 23‐day lactation period. At weaning, eight dams were sacrificed to establish baseline values, while the remaining dams were returned to 0.4% calcium and treated with vehicle (saline), sodium fluoride (NaF), zoledronic acid (ZA), or sclerostin antibody (Scl‐Ab) for either 7 or 28 days (eight animals per group per time point). Femora were examined by μCT, dynamic histomorphometry, Fourier transform infrared imaging, and three‐point bending of notched specimens. Cortical porosity decreased in all groups from baseline to day 28. Intracortical mineralizing surface (MS/BS) and mineral apposition rate (MAR), as well as the mineral‐to‐matrix ratio were unaffected by treatment, but intracortical crystallinity was increased in the ZA group at day 10 compared with vehicle. Cortical area increased in all groups over 28 days mainly because of an addition of bone at the endocortical surface. Endocortical MS/BS did not vary among the groups, but endocortical MAR was suppressed in the NaF group at day 2 and elevated in the Scl‐Ab group at day 4 compared with vehicle. Endocortical mineral‐to‐matrix ratio was increased at days 5 and 10 following NaF treatment and endocortical crystallinity was increased at day 5 following ZA treatment compared with vehicle. Fracture toughness did not differ among the groups. Thus, the treatments affected matrix maturation more strongly at the endocortical then intracortical envelope. In this model of induced remodeling, the bone formation phase is synchronized at multiple sites, facilitating study of the effects of drugs or other bone‐targeting agents on matrix maturation independent of their effects on the initiation of remodeling. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: A randomized study comparing intermittent treatment and an ADFR regime

Cited by 56 publications

References 37 publications

Suppressed Bone Turnover by Bisphosphonates Increases Microdamage Accumulation and Reduces Some Biomechanical Properties in Dog Rib

Suppressed Bone Turnover by Bisphosphonates Increases Microdamage Accumulation and Reduces Some Biomechanical Properties in Dog Rib

A Meta-analysis of Etidronate for the Treatment of Postmenopausal Osteoporosis

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

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