Risk factors for prediction of inadequate response to antiresorptives

Abstract

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross-sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous antiosteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx TM ) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture ( p ¼ 0.005), two or more falls in the previous year ( p ¼ 0.032), low lumbar spine bone mineral density (BMD) ( p ¼ 0.02), 25 hydroxyvitamin D ( p ¼ 0.017), and hip ImaTx fracture load index ( p ¼ 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47-8.82; p ¼ 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55-9.77; p ¼ 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI,; p ¼ 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem. ß

Assessment criteria for vitamin D deficiency/insufficiency in Japan — proposal by an expert panel supported by Research Program of Intractable Diseases, Ministry of Health, Labour and Welfare, Japan, The Japanese Society for Bone and Mineral Research and The Japan Endocrine Society [Opinion]

“…Reports from other countries indicated serum 25(OH)D levels less than 30-32 ng/mL were associated with poorer BMD responses to bisphosphonates and selective estrogen receptor modulators or with increased fracture incidence during anti-osteoporotic pharmaceutical treatment [25][26][27][28].…”

Osteoporoz Tedavisine Yetersiz Yanıt

“…Tedavi sırasında KMY'de önemli bir kayıp, kemik döngüsü belirteçlerinin düzeyinde beklenmeyen değişiklik ya da kırık gelişmesi durumunda genellikle tedaviye yetersiz yanıt olduğu kabul edilir ve farklı bir tedaviye geçilebilir. Tedaviye yetersiz cevabın tahmin edilmesinde; frajilite kırığı öyküsü, düşük 25(OH)vitamin D seviyeleri (<20 ng/mL) ve proksimal femurlarının yapısal analizlerinde ölçülen düşük kırık yükü önemli değişkenler olarak belirlenmiştir (20). Benzer şekilde, bir başka çalışmada da düşük vitamin D seviyeleri zayıf tedaviye cevap ile ilişkili bulunmuştur (21).…”

“…OP tedavisi altında hastalarda yeni kırıklar ortaya çıkmamış, KMY değerleri yükselmiş ve kemik belirteçleri antirezorptif • Erkeklerde serbest testosteron, gonadotropin ve prolaktin tedaviden beklenen ölçüde azalmış ise (denosumab ile en büyük, raloksifen veya kalsiyum desteği ile en küçük) tedaviye devam edilmelidir. Aksine, tedavinin başlangıcından bir yıl sonra bu bahsi geçen kriterler sağlanamamışsa, kullanılan ilacın değiştirilmesi düşünülmelidir (20). Bununla birlikte, ilacı kullanım şekli ve tedaviye uyumu hastaya sorulup, eğer bunlarda herhangi bir sorun yoksa sekonder faktörler açısından değerlendirildikten sonra ilacın değiştirilmesi daha uygun olacağı da unutulmamalıdır.…”

Factores relacionados con la respuesta inadecuada al tratamiento osteoformador (teriparatida/PTH 1-84) en pacientes con osteoporosis severa: resultados preliminares

“…However, in routine clinical practice, therapeutic failure is relatively common, particularly when assessed individually. In this sense, between 18 and 35% of patients treated with antiresorptive medications, mainly bisphosphonates (depending on the criteria) have a failure response and/or inadequate response to treatment [1][2][3] . Although nonadherence is often one of the main causes of inadequate response, other factors such as comorbidities, previous osteoporosis treatment, disease severity or vitamin D deficiency, among others, may influence response to antiosteoporotic treatment [1][2][3] .…”

“…In this sense, between 18 and 35% of patients treated with antiresorptive medications, mainly bisphosphonates (depending on the criteria) have a failure response and/or inadequate response to treatment [1][2][3] . Although nonadherence is often one of the main causes of inadequate response, other factors such as comorbidities, previous osteoporosis treatment, disease severity or vitamin D deficiency, among others, may influence response to antiosteoporotic treatment [1][2][3] . Similarly, bone forming treatment with parathyroid hormone (PTH) and/or teriparatide has been associated with a marked increase in BMD, as high as 10.5% at the lumbar spine after 18 months of treatment, and a decrease in the incidence of vertebral fractures (65%) [4][5][6] .…”