Alendronate and Estrogen Effects in Postmenopausal Women with Low Bone Mineral Density

Bone, Henry G.; Greenspan, Susan L.; McKeever, C; Bell, Norman H.; Davidson, Michael; Downs, Robert W.; Emkey, Ronald; Meunier, Pierre J.; Miller, Sam S.; Mulloy, Anthony L.; Recker, Robert R.; Weiss, Stuart; Heyden, Norman; Musliner, Thomas; Suryawanshi, Shailaja; Yates, A.J.P.; Lombardi, Antonio

doi:10.1210/jc.85.2.720

Cited by 181 publications

(200 citation statements)

References 19 publications

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“…Both bisphosphonates and HRT have been shown to increase BMD in postmenopausal women and in men with osteoporosis (Liberman et al, 1995;Bone et al, 2000;Orwoll et al, 2000). Significant reductions in vertebral and non-vertebral fracture rates in postmenopausal women have been reported after only 1 year of treatment (Ensrud et al, 1997;Harris et al, 1999;Pols et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Gandhi¹,

Lekamwasam

Inman³

et al. 2003

Br J Haematol

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Summary. Reduced bone mineral density (BMD) has been reported following allogeneic stem cell transplantation (alloSCT) but the effects of autologous SCT (autoSCT) are less well characterized. We performed a prospective study of BMD changes and its determinants in 44 SCT recipients (38 auto and six allo; 30 peripheral blood SCT and 14 bone marrow transplantation). Serial measurements of BMD at the lumbar spine and femoral neck were performed at baseline and at 3, 6, 12 and 24 months, and spinal radiographs were performed at baseline and 12 months. Mean baseline BMD values at the femoral neck and spine were within normal limits. At 3 months, there was a significant decline of BMD at the femoral neck (P ¼ 0AE011) and a nonsignificant trend towards reduction at the spine. BMD loss persisted for up to 2 years at the femoral neck (P ¼ 0AE005), but values returned to baseline at the spine. Reflecting the rapid initial decline in BMD, bone-specific alkaline phosphatase (a serum marker of bone formation) showed a significant initial decline at 1 month but had recovered to pretransplant levels by 3 months. No new fractures were detected at 1 year post transplant. Sex, diagnosis, use of total body irradiation, stem cell source and type of graft (auto versus allo) did not significantly predict BMD change over the first 12 months. In conclusion, significant and persistent bone loss at the femoral neck was demonstrated in this group of patients following stem cell transplantation. The implications of these findings for future fracture risk require further study.

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Section: Discussionmentioning

confidence: 99%

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Gandhi¹,

Lekamwasam

Inman³

et al. 2003

Br J Haematol

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“…However, only a few reports have included histology or histomorphometry of bone taken from or close to the subtrochanteric fracture site. Iliac crest biopsies generally have revealed extremely low bone turnover, a finding consistent with BP treatment, (137--139) especially in patients treated concomitantly with a BP and another antiresorptive agent, such as estrogen, (140) or with BPs and GCs. (141) The overall hierarchy of evidence quality for a case would be based on the quality of these seven areas:…”

Section: Atypical Subtrochanteric and Femoral Shaft Fractures: Clinicmentioning

confidence: 92%

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

998

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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“…Small additional increments in BMD occurred when bisphosphonates were combined with estrogen or raloxifene (87)(88)(89), but the effects of these agents are not additive or synergistic. Whether combination therapy provides additional fracture protection is unproven.…”

Section: Combining Bisphosphonates With Other Antiresorptive Agentsmentioning

confidence: 95%

Bisphosphonates

McClung

2006

Arq Bras Endocrinol Metab

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Osteoporosis is the result of bone loss due to an imbalance in bone turnover such that bone resorption exceeds bone formation. Bisphosphonates are potent inhibitors of osteoclast activity that reduce bone turnover and re-establish the balance between bone resorption and formation. In clinical studies, several bisphosphonates prevent bone loss, preserve bone structure, improve bone strength and, in patients with osteoporosis, substantially reduce fracture risk. They are effective in multiple clinical settings including postmenopausal osteoporosis, low bone mass in men and drug-induced bone loss. Intermittent oral dosing and intravenous administration are more convenient than the original daily dosing regimen. These drugs are generally well tolerated and have an excellent safety profile in that serious side effects are uncommon. Potent bisphosphonates are generally the preferred treatment option for most patients with or at risk for osteoporosis. RESUMO Bisfosfonatos.Osteoporose é o resultado da perda óssea devida a um imbalanço no turnover ósseo, onde a reabsorção óssea excede sua formação. Os bisfosfonatos são inibidores potentes da atividade osteoclástica, que reduzem o turnover ósseo e restabelecem o balanço entre a reabsorção e a formação óssea. Em estudos clínicos, vários bisfosfonatos previnem a perda óssea, preservam sua estrutura, melhoram sua força e substancialmente reduzem o risco de fraturas em pacientes com osteoporose. Eles são efetivos em várias situações clínicas, incluindo a osteoporose pós-menopáusica, a reduzida massa óssea em homens e perda óssea induzida por drogas. Doses orais intermitentes e administração intravenosa são mais convenientes do que o esquema original de doses diárias. Essas drogas são geralmente bem toleradas e têm um excelente perfil de segurança, no qual efeitos colaterais sérios são incomuns. Os bisfosfonatos potentes são geralmente a opção terapêutica preferida para a maioria dos pacientes com ou em risco de osteoporose. O STEOPOROSIS IS A DISORDER of skeletal fragility due a combination of low bone mass, deteriorated bone architecture and perhaps alterations in other aspects of bone quality (1). Osteoporosis is usually the result of bone loss that occurs after menopause in women and in older men and women. This bone loss is a consequence of increased and unbalanced bone review article Bisphosphonates

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Alendronate and Estrogen Effects in Postmenopausal Women with Low Bone Mineral Density

Cited by 181 publications

References 19 publications

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

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

Bisphosphonates

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