Changes in bone density and turnover after alendronate or estrogen withdrawal

Wasnich, Richard D.; Bagger, Yu Z.; Hosking, David J.; McClung, Michael R.; Wu, Mei; Mantz, Ann Marie; Yates, John; Ross, Philip D.; Alexandersen, Peter; Ravn, Pernille; Christiansen, Claus; Santora, Arthur C.

doi:10.1097/01.gme.0000123641.76105.b5

Cited by 112 publications

(71 citation statements)

References 41 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

228

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

228

147

View full text Add to dashboard Cite

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“…The mean changes in BMD in the group that discontinued HT were -7.7% at the spine and -5.2% at the hip. The mean BMD at the end of 6 years was similar to baseline at the end of 6 years in the HT-treated group that discontinued medication (57).…”

Section: Discontinuation Of Estrogen Therapymentioning

confidence: 63%

Estrogen therapy for postmenopausal osteoporosis

Fitzpatrick

2006

Arq Bras Endocrinol Metab

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Osteoporosis is a worldwide problem that results in fractures that lead to disability and high costs to society. Estrogen therapy is frequently utilized for postmenopausal symptoms, but also has proven protective effects on the skeleton. The main action of estrogen at the cellular level is to inhibit the osteoclast by increasing levels of osteoprotegerin (OPG). OPG binds to the receptor activator of NFkB and prevents osteoclast differentiation, activity and survival. Numerous trials have demonstrated the positive effect estrogen has on the improvement of bone mineral density, and lower doses have also proven efficacious with fewer side effects. Both observational and randomized clinical trials have demonstrated the ability of estrogen treatment to prevent fractures. Topics that remain controversial include the appropriate length of estrogen treatment for postmenopausal women and the appropriate follow-up after treatment discontinuation. RESUMO Terapia Estrogênica Para Osteoporose na Pós-Menopausa.Osteoporose é um problema universal que resulta em fraturas e leva a incapacidade e alto custo para a sociedade. A terapia estrogênica é freqüentemente utilizada nos sintomas da pós-menopausa, mas também tem comprovado efeito protetor no esqueleto. A principal ação a nível celular é inibir os osteoclastos por causa do aumento dos níveis de osteoprotegerina (OPG). A OPG liga-se ao receptor ativador do NFkB e impede a diferenciação, atividade e sobrevida dos osteoclastos. Numerosos estudos demonstraram o efeito positivo do estrogênio na melhora da densidade mineral óssea e doses mais baixas apresentam comprovada eficácia com menos efeitos colaterais. Tanto os estudos observacionais como os clínicos demonstraram a capacidade da terapia estrogênica na prevenção de fraturas. Alguns tópicos permanecem em controvérsia, como a terapia prolongada e um seguimento adequado após a descontinuação do tratamento.

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“…A prospective study covering the peri-menopausal transition in healthy women suggests that changes in bone turnover occur during the late pre-menopause with a decrease in bone formation, which only later is followed by a rise in bone resorption (25). It is now widely accepted that the accelerated rate of bone loss seen after the menopause is mainly due to an uncoupling in bone turnover and an increase in bone resorption (26,27). Studies employing specific bone markers indicate that bone turnover continues to be increased (and to be associated with bone loss) during late menopause (28)(29)(30)(31)(32)(33).…”

Section: Menopause and Ageingmentioning

confidence: 99%

Clinical application of biochemical markers of bone turnover

Seibel

2006

Arq Bras Endocrinol Metab

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With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This review provides an overview of the current evidence regarding the clinical use of biochemical markers of bone remodelling in bone disease, with an emphasis on osteoporosis. RESUMO Marcadores Bioquímicos da Remodelação Óssea.Tendo em vista o crescimento da população idosa na maioria dos paí-ses, os distúrbios do metabolismo ósseo e mineral estão tornando-se cada vez mais relevantes na prática clínica diária. Conseqüentemente, o interesse e a necessidade de medidas efetivas para serem usadas no rastreamento, diagnóstico e seguimento de tais patologias vêm crescendo acentuadamente. Além da avaliação clínica e de técnicas de imagens, os marcadores bioquímicos desempenham um importante papel na avaliação e diagnóstico das doenças ósseas metabólicas. Recentemente, a melhor caracterização dos componentes intracelulares e extracelulares da matriz óssea resultou no desenvolvimento dos marcadores moleculares, os quais refletem tanto a formação como a reabsorção óssea. Estes marcadores bioquímicos não são invasivos e comparativamente são de mais baixo custo, e quando aplicados e interpretados corretamente são instrumentos úteis no diagnóstico e tratamento das doenças ósseas metabólicas. Esta revisão abordará evidências atuais, levando em consideração o uso clínico dos marcadores bioquímicos da remodelação óssea nas doenças metabólicas ósseas, com ênfase na osteoporose.

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Changes in bone density and turnover after alendronate or estrogen withdrawal

Abstract: Alendronate produces greater residual skeletal effects than estrogen-progestin after therapy discontinuation.

Cited by 112 publications

References 41 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

Estrogen therapy for postmenopausal osteoporosis

Clinical application of biochemical markers of bone turnover

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