Which is the best antiresorptive treatment after finishing teriparatide? / ¿Cuál es el mejor tratamiento antirresortivo luego de terminar con teriparatide?

Abstract Anabolic drugs are the treatment of choice for osteoporotic patients with very high risk of fractures. Post anabolic treatment with an antiresorptive drug maintains the bone mineral density (BMD) gained. The recommendations regarding the ideal antiresorptive drug are not precise. The aim of this paper is to compare the usefulness of zoledronate and denosumab in a group of 28 women with very high risk of fractures. All of them completed at least one year of treatment with teripatide and latter 14 received zolendronate and 14 denosumab for another year. We retrospectively review their biochemical and densitometric changes. Both treat ment groups experienced a reduction in bone turnover markers of the same magnitude at the end of the second year. In Lumbar Spine BMD increase of 3.96 ± 8.56% Median (Me) 2.54 p = 0.21 in zolendronate group and 3.55 ± 5.36% (Me 5.14) p = 0.07 in denosumab group. Femoral Neck BMD changed -0.09 ± 6.50% (Me 0.29) p = 0.85 in zolendronate group, and - 3.41 ± 5.08% (Me 5.35) p = 0.59 in denosumab group, with no difference between both groups. In Total Hip BMD an increase of 0.55 ± 4.20% (Me 0.43) p = 0.70 in zoledronate group, and 4.53 ± 5.13% (Me 0.64) p = 0.04 with denosumab. We conclude that both antiresortive treatments have a similar effect in biochemical markers after one year of treatment. BMD increase significantly in total hip and changed with a trend toward in lumbar spine with denosumab, but without differences between both groups of treatment.

Resumen Los anabólicos son el tratamiento de elección en la osteoporosis con muy alto riesgo de fracturas. Después del tratamiento anabólico un fármaco antirresortivo mantiene la densidad mineral ósea (DMO) ganada. Las reco mendaciones sobre el fármaco antirresortivo ideal no son precisas. El objetivo de este trabajo es comparar la utilidad de zoledronato y denosumab en un grupo de 28 mujeres con muy alto riesgo de fracturas. Todas ellas completaron al menos un año de tratamiento con teripatide y luego 14 recibieron zolendronato y 14 denosumab durante un año. Revisamos retrospectivamente sus cambios bioquímicos y densitométricos. Ambos grupos de tratamiento experimentaron una reducción de los marcadores de recambio óseo de la misma magnitud al final del segundo año. En columna lumbar la DMO aumentó 3.96 ± 8.56% Mediana (Me) 2.54, p = 0.21 en el grupo zolendronato y 3.55 ± 5.36% (Me 5.14) p = 0.07 en el grupo denosumab. La DMO del cuello femoral cambió -0.09 ± 6.50% (Me 0.29) p = 0.85 en el grupo zolendronato y - 3.41 ± 5.08% (Me 5.35) p = 0.59 en el grupo de denosumab, sin diferencias entre ambos grupos. En la Cadera Total la DMO aumentó 0.55 ± 4.20% (Me 0.43) p = 0.70 con zoledronato y 4.53 ± 5.13% (Me 0.64) p = 0.04 con denosumab. Concluimos que ambos tratamien tos antiresortivos tuvieron un efecto similar en los marcadores bioquímicos después de un año de tratamiento. La DMO aumentó significativamente en la cadera total y mostró una tendencia similar en columna lumbar con denosumab, sin diferencias entre ambos tratamientos.

Current Challenges in Osteoporosis Treatment Discontinuation

@#Osteoporosis is a chronic disease that may require lifelong therapy. Therefore, evidence-based approach regarding the efficacy and safety of long‐term osteoporosis therapy and therapy discontinuation is important. The most important goals for osteoporosis and fragility fracture patients are the recovery of pre-fracture functional level and reduction of fracture risk. There has been increasing consensus that a treat-to-target (T2T) strategy is applicable to osteoporosis and that bone mineral density (BMD) is currently the most clinically appropriate target. However, there is no clear consensus with regard to the definition of a specific BMD treatment target and timeframes applicable to T2T in osteoporosis, and these would need to be individually determined. Treatment with bisphosphonates may be interrupted after 3-5 years, only in patients in whom fracture risk is low or lowered because of the treatment itself. It is recommended never to discontinue treatment in patients with one or more prevalent osteoporotic fractures or in whom the BMD values are still below -2.5 (T score). Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures. Patients considered at high fracture risk should either continue denosumab therapy for up to ten years or be switched to an alternative treatment. For patients at low-risk, a decision to discontinue denosumab could be made after five years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover.

Postmenopausal Osteoporosis: Diagnosis, FRAX® and Management

@#Osteoporosis-related fractures are increasing at a rapid rate, especially in Asia due to the ageing population. This would result in increased morbidity and mortality of the seniors as well as creating a strain on the healthcare system. Efforts should be made to prevent osteoporosis, screen for osteoporosis early and timely treatment to reduce the risk of fractures. As falls are a major risk factor for fracture in osteoporotic patients, management of osteoporosis should include efforts to reduce falls. Using a population-wide strategy for women 65 years old couple with high-risk population screening using a combination of tools such as FRAX® and OSTA as well as clinical risk factors for women below 65 years old can detect osteoporosis early for intervention. Treatment options for osteoporosis include bisphosphonates, denosumab, teriparatide, raloxifene, menopausal hormone therapy and tibolone. Drug choices should be individualised to the patient, balancing the risk/benefit ratio.

Treatment of postmenopausal osteoporosis: a literature-based algorithm for use in the public health care system / Tratamento da osteoporose pós-menopáusica: um algoritmo baseado na literatura para uso no sistema público de saúde

ABSTRACT Bisphosphonates are considered first-line agents in the treatment of postmenopausal osteoporosis based on extensive experience of use, safety, and proven efficacy in reducing vertebral, non-vertebral and femur fractures. However, post-marketing reports based on the treatment of millions of patients/year over lengthy periods of time have revealed the occurrence of initially unexpected adverse effects, such as osteonecrosis of the jaw and atypical femoral fracture, leading to the restriction of treatment duration with bisphosphonates by global regulatory agencies. However, despite the association between these effects and bisphosphonates, this risk should be analyzed in the context of osteoporosis treatment, alongside the benefit of preventing osteoporotic fractures and their clinical consequences. Therefore, we consider it plausible to discuss the restriction to the use of bisphosphonates, possible indications for prolonged treatment and alternative therapies following the suspension of this drug class for patients with persistent high risk of fracture after initial treatment, especially considering the problems of public health funding in Brazil and the shortage of drugs provided by the government. Thus, to standardize the treatment of osteoporosis in the public health care system, we aim to develop a proposal for a scientifically-based pharmacological treatment for postmenopausal osteoporosis, establishing criteria for indication and allowing the rational use of each pharmacological agent. We discuss the duration of the initial bisphosphonate treatment, the therapeutic options for refractory patients and potential indications of other classes of drugs as first-choice treatment in the sphere of public health, in which assessing risk and cost effectiveness is a priority.

RESUMO Com base na vasta experiência de uso, segurança e eficácia comprovada na redução de fraturas vertebrais, não vertebrais e femorais, os bisfosfonatos são considerados agentes de primeira linha no tratamento da osteoporose pós-menopáusica. No entanto, os relatos pós-venda baseados no tratamento de milhões de pacientes/ano durante períodos prolongados de tempo revelaram a ocorrência de efeitos adversos inicialmente inesperados, como osteonecrose da mandíbula e fratura atípica do fêmur. Isso levou as agências reguladoras globais a restringirem a duração do tratamento com bisfosfonatos. No entanto, apesar da associação entre esses efeitos e os bisfosfonatos, esse risco deve ser analisado no contexto do tratamento da osteoporose, paralelamente ao benefício na prevenção de fraturas osteoporóticas e suas consequências clínicas. Portanto, considera-se plausível discutir a restrição ao uso dos bisfosfonatos, possíveis indicações para o tratamento prolongado e terapias opcionais após a suspensão dessa classe de fármaco para pacientes com alto risco persistente de fratura após o tratamento inicial, especialmente se considerarmos os problemas financeiros de saúde pública no Brasil e a escassez de fármacos fornecidos pelo governo. Assim, para padronizar o tratamento da osteoporose no sistema público de saúde pretende-se desenvolver uma proposta de tratamento farmacológico cientificamente fundamentada para a osteoporose pós-menopáusica, estabelecer critérios de indicação e permitir o uso racional de cada agente farmacológico. Discutem-se a duração do tratamento inicial com bisfosfonatos, as opções terapêuticas para pacientes refratários e potenciais indicações de outras classes de medicamentos como tratamento de primeira linha na esfera da saúde pública, em que a avaliação do risco e custo-efetividade é uma prioridade.

Bisphosphonates in the treatment of metabolic bone diseases / Atualização sobre bisfosfonatos nas doenças osteometabólicas

Osteoporosis is a disease characterized by low bone mass associated with the deterioration of microarchitecture, due to an imbalance either in high bone resorption or low bone formation or in both, leading to a high risk of fractures. Bisphosphonates are medications which reduce the ability of osteoclasts to induce bone resorption and consequently improve the balance between resorption and formation. There are bisphosphonates approved for the prevention and treatment of osteoporosis. Administration can be oral (daily, weekly or monthly) or intravenous (quarterly or yearly). These medications are well tolerated and with the correct instructions of administration have a good safety profile. Serious side effects, such as, osteonecrosis of jaw is very rare. Bisphosphonates are the most prescribed medication for the treatment of osteoporosis.

Osteoporose é uma doença caracterizada por baixa massa óssea associada à deterioração da microarquitetura devido ao desbalanço pela alta reabsorção, baixa formação ou ambas, levando a um alto risco de fraturas. Bisfosfonatos são medicamentos que reduzem a capacidade de os osteoclastos induzirem a reabsorção óssea e, consequentemente, melhorar o balanço entre reabsorção e formação. Há bisfosfonatos aprovados para prevenção e tratamento da osteoporose. A administração pode ser via oral (diária, semanal ou mensal) ou intravenosa (trimestral ou anual). Essas medicações são bem toleradas e, seguindo as recomendações adequadas, apresentam alto grau de perfil de segurança. Efeitos colaterais sérios, como osteonecrose de mandíbula, são raros. Bisfosfonatos são as medicações mais prescritas para o tratamento da osteoporose.

The clinical and epidemiologic consequences of redefining treatment criteria: who should be treated?: [review] / Consecuencias clínicas y epidemiológicas de la redefinición de criterios de tratamiento: ¿quién debe tratarse?: [revisión]

Bone mineral density (BMD) is the tool for diagnosing osteoporosis in older adults. However, BMD alone is not sufficient for deciding who should be given treatment at either the individual patient or the public health level. Robust, scientifically validated algorithms that combine BMD with other clinical risk factors provide more accurate assessment of fracture probability. New guidelines for managing osteoporosis are now based on the assessment of absolute fracture risk, not simply on bone mineral density values. Accordingly, treatment resources will be redirected away from young postmenopausal women with low BMD and low fracture risk toward older adults at moderate or high risk for fracture. It is expected that, with these algorithms, the cost and effectiveness of medical care for patients with osteoporosis will be improved.

La densidad mineral ósea (DMO) es la herramienta de diagnóstico para osteoporosis en adultos mayores. Sin embargo, por sí sola la DMO no es suficiente para decidir quién debe recibir tratamiento ni al nivel del paciente individual ni al nivel de salud pública. Los algoritmos robustos, científicamente comprobados, que combinan DMO con otros factores de riesgo clínicos proporcionan una evaluación más precisa de la probabilidad de fractura. Los nuevos lineamientos para el manejo de la osteoporosis se basan en la evaluación del riesgo de fractura absoluto, no ya tan sólo en los valores de densidad mineral ósea. Por lo tanto, los recursos para el tratamiento cambiarán, de dirigirse a mujeres postmenopáusicas jóvenes con baja DMO y bajo riesgo de fractura, a mujeres mayores con riesgo de fractura alto o moderado. Se espera que con estos algoritmos haya una mejora en cuanto al costo y la efectividad de la atención médica para pacientes con osteoporosis.

Characteristics of osteoporosis-related fracture and clinical study / 基础医学与临床

Bone fracture is the most serious outcome of osteoporosis,the morbidity has been linked to age,gender and races.The characteristics of osteoporotic fracture include reduced bone quality,a delay in bone fracture union process,and a high incidence of re-fracture.The therapy of osteoporotic fracture includes surgical management and osteoporosis treatment.Osteoporosis treatment can improve bone quantity and bone quality,decrease the rate of fracture.The rule of surgical management is simpleness,safety,and efficacy.Because of poor bone quality,internal fixation and implant are easy lossened.Ideas for future research,such as development of a new implant with rigidity and elasticity like bone tissue,development of a new drug which can improve bone mass and quality quickly.Regardless of surgical management for osteoporotic fracture,pharmacological treatment of osteoporosis is also necessary.In order to get a good outcome of osteoporotic fracture treatment,both surgical management and osteoporosis treatment are important.