Current perspective on antiresorptive therapies in osteoporosis

Öz

Antiresorptive drugs act by suppressing bone turnover and reduce the risk of fracture by increasing the amount of bone over time. Today, the main antiresorptive drugs with indications for use in the treatment of osteoporosis are bisphosphonates, denosumab, and a selective estrogen receptor modulator(SERM), raloxifene. Bisphosphonates are used as first-line drugs in the treatment of osteoporosis and reducing the risk of fractures. Bisphosphonates accumulate in bone and their effects on bone turnover may persist for years after discontinuation of the drug. The most important side effects that can be seen in patients using bisphosphonates associated with long-term suppression of bone turnover are osteonecrosis of the jaw and atypical femur fractures. It is possible to prevent these problems by not using bisphosphonates continuously for a long time without interrupting the treatment in patients with low fracture risk. Denosumab inhibits bone turnover by impairing osteoclast functions. It increases the bone mineral density (BMD) and provides reduction in fracture risk. One of the drawbacks with the use of denosumab is the rapid decrease in effects on bone and an increased risk of bone loss and fracture after discontinuation of treatment. Denosumab should not be discontinued or the treatment be continued with a different antiresorptive such as bisphosphonates. Although denosumab can be used in patients with renal failure, it has a high risk of causing hypocalcemia. Of the selective estrogen receptor blockers (SERMs), only raloxifene is currently used very limitedly in the treatment of osteoporosis. Although raloxifene increases bone mineral density in the spine and hip and reduces the risk of vertebral fractures, its effect on non-vertebral fractures has not been demonstrated. Since it has a strong antiestrogenic effect in the breast, it may reduce the risk of invasive breast cancer in estrogen receptor (ER) positive patients. Raloxifene has a limited indication for use in the treatment of osteoporosis in postmenopausal women at high risk for invasive breast cancer, as well as in postmenopausal women who are intolerant or unsuitable for bisphosphonates and do not have a fragility fracture.

Anahtar Kelimeler

• osteoporosis
• antiresorptive
• therapy

Osteoporozda antirezorptif tedavilere güncel yaklaşım

Öz

Antirezorptif ilaçlar kemik döngüsünü baskılayarak etkinlik gösteren ve zamanla kemik miktarında artışa neden olarak kırık riskini azaltan bir ilaç grubudur. Günümüzde osteoporoz tedavisinde kullanım endikasyonu bulunan başlıca antirezorptif ilaçlar bisfosfonatlar, denosumab ve selektif östrojen reseptör modülatörlerinden raloksifendir. Bisfosfonatlar osteoporozun tedavisinde ve kırık riskini azaltmada ilk basamak olarak kullanılır. Kemikte birikime uğrarlar ve kemik döngüsü üzerindeki etkileri ilacın kesilmesinden sonra yıllarca sürebilir. Kemik döngüsünün uzun süreli baskılanmasına bağlı bisfosfonat kullanan hastalarda görülebilen en önemli yan etkiler çene kemiği osteonekrozu ve atipik femur kırıklarıdır. Kırık riski düşük olan hastalarda bisfosfonatların aralıksız uzun süre kullanılmamaları ve tedaviye ara verilmesi ile bu sorunların önlenmesi mümkündür. Denosumab osteoklast fonksiyonlarını bozarak kemik döngüsünü inhibe eder. Kemik miktarını artırır ve kırık riskinde azalma sağlar. Denosumab ile ilgili çekincelerden birisi tedavinin kesilmesini takiben kemik üzerindeki etkilerin hızla azalması ve kemik kütlesinde kayıp ve kırık riskinde artış olmasıdır. Denosumab tedavisine ara verilmemesi veya tedavinin kesilmesini takiben bisfosfonatlar gibi farklı bir antirezorptif ile tedaviye devam edilmesi bu riski azaltabilir. Denosumab renal yetmezlikli hastalarda kullanılabilirse de hipokalsemiye yol açma riski yüksektir. Selektif östrojen reseptör blokerlerinden(SERM) sadece raloksifen günümüzde osteoporoz tedavisinde çok kısıtlı olarak kullanılmaktadır. Raloksifen vertebra ve kalçada kemik mineral yoğunluğunda artış sağlar ve vertebra kırık riskini azaltırsa da vertebra dışı kırıklar üzerine etkisi gösterilememiştir. Memede güçlü antiöstrojenik etki gösterdiğinden östrojen reseptörü(ER) pozitif hastalarda invaziv meme kanseri riskinde azalma sağlayabilir. Raloksifenin invaziv meme kanseri riski yüksek olan ve yanı sıra bisfosfonatları tolere edemeyen veya bu tedavilere uygun olmayan ve frajilite kırığı bulunmayan postmenopozal kadınlarda osteoporozun tedavisinde sınırlı bir kullanım endikasyonu vardır.

Anahtar Kelimeler

• osteoporoz
• antirezorptif
• tedavi

Kaynakça

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