Significant Differential Effects of Alendronate, Estrogen, or Combination Therapy on the Rate of Bone Loss after Discontinuation of Treatment of Postmenopausal Osteoporosis

Greenspan, Susan L.; Emkey, Ronald; Bone, Henry G.; Weiss, Stuart; Bell, Norman H.; Downs, Robert W.; McKeever, C; Miller, Sam S.; Davidson, Michael; Bolognese, Michael A.; Mulloy, Anthony L.; Heyden, Norman; Wu, Mei; Kaur, Amandeep; Lombardi, Antonio

doi:10.7326/0003-4819-137-11-200212030-00008

Cited by 194 publications

(78 citation statements)

References 20 publications

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“…There was an initial rapid loss in BMD over 6 months, eventually leveling off to near-baseline levels. These data are more similar to the findings with hormone-replacement therapy, (21)(22)(23)(24) denosumab, (25) and parathyroid hormone (26) than (12) with the bisphosphonate group of drugs. This rapid resolution of effect is consistent with the fact that the inhibition of catK by ODN is effectively reversible.…”

Section: Discussionsupporting

confidence: 84%

Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three-year continued therapy and resolution of effect

Eisman

Bone²,

Hosking

et al. 2010

Journal of Bone and Mineral Research

229

147

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The selective cathepsin K inhibitor odanacatib (ODN) progressively increased bone mineral density (BMD) and decreased boneresorption markers during 2 years of treatment in postmenopausal women with low BMD. A 1-year extension study further assessed ODN efficacy and safety and the effects of discontinuing therapy. In the base study, postmenopausal women with BMD T-scores between À2.0 and À3.5 at the lumbar spine or femur received placebo or ODN 3, 10, 25, or 50 mg weekly. After 2 years, patients (n ¼ 189) were rerandomized to ODN 50 mg weekly or placebo for an additional year. Endpoints included BMD at the lumbar spine (primary), total hip, and hip subregions; levels of bone turnover markers; and safety assessments. Continued treatment with 50 mg of ODN for 3 years produced significant increases from baseline and from year 2 in BMD at the spine (7.9% and 2.3%) and total hip (5.8% and 2.4%). Urine cross-linked N-telopeptide of type I collagen (NTx) remained suppressed at year 3 (À50.5%), but bone-specific alkaline phosphatase (BSAP) was relatively unchanged from baseline. Treatment discontinuation resulted in bone loss at all sites, but BMD remained at or above baseline. After ODN discontinuation at month 24, bone turnover markers increased transiently above baseline, but this increase largely resolved by month 36. There were similar overall adverse-event rates in both treatment groups. It is concluded that 3 years of ODN treatment resulted in progressive increases in BMD and was generally well tolerated. Bone-resorption markers remained suppressed, whereas bone-formation markers returned to near baseline. ODN effects were reversible: bone resorption increased transiently and BMD decreased following treatment discontinuation. ß

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Section: Discussionsupporting

confidence: 84%

Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three-year continued therapy and resolution of effect

Eisman

Bone²,

Hosking

et al. 2010

Journal of Bone and Mineral Research

229

147

View full text Add to dashboard Cite

show abstract

“…Black et al recently noted similar non-vertebral fracture reduction in women continuing alendronate and those stopping therapy after 5 years of treatment [27]. Conversely, others noted that discontinuing HRT had a different impact on BMD than did discontinuing alendronate or combination therapy [28].…”

Section: Discussionmentioning

confidence: 88%

Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women

Langsetmo¹,

Morin

Richards

et al. 2008

Osteoporos Int

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Summary-Observational studies are needed to quantify real-life effectiveness of antiresorptive therapy in the prevention of clinical fractures. Antiresorptive therapies were associated with an overall 32% reduction in low-trauma non-vertebral fracture risk among women 50 and older. Effectiveness may be lower among older women and those without risk factors.Introduction-Randomized controlled trials have shown that antiresorptive therapies reduce the risk of fracture in selected populations, but further study is needed to quantify their real-life effectiveness. The study objective was to determine the association between antiresorptive use and low-trauma nonvertebral fracture in women 50 and older.

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“…Within the first year of stopping alendronate or risedronate after 2 years of treatment in early postmenopausal women, indices of bone turnover returned toward baseline, and bone loss resumed at a rate similar to the control group (39,85). In contrast, discontinuing alendronate therapy in older women who were treated with alendronate for two to five years resulted in stable BMD and persistent suppression of bone turnover for up to 5 years (11,32,86). This raises the possibility of limiting alendronate therapy to five years.…”

Section: How Long Bisphosphonate Treatment Be Continued?mentioning

confidence: 78%

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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Significant Differential Effects of Alendronate, Estrogen, or Combination Therapy on the Rate of Bone Loss after Discontinuation of Treatment of Postmenopausal Osteoporosis

Abstract: Accelerated bone loss is seen after withdrawal of estrogen therapy but not after withdrawal of alendronate or combination therapy. The differential effects after withdrawal of therapy should be considered in the management of postmenopausal osteoporosis.

Cited by 194 publications

References 20 publications

Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three-year continued therapy and resolution of effect

Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three-year continued therapy and resolution of effect

Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women

Bisphosphonates

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