Bifosfonatlar ve Çenelerde Görülen Osteonekroz

Yıl 2022, Cilt: 12 Sayı: 2, 345 - 351, 17.05.2022

Büşra Tanrıkol Güldane Mağat

https://doi.org/10.33631/sabd.1115442

Öz

Bifosfonatlar, stabil kemik mineralizasyonu düzenlerler.Endojen inorganik pirofosfatların analoglarıdır. Bifosfonatların osteoklastları inaktive ederek osteoklastik kemik rezorbsiyonunu azalttığı bilinmektedir. Bu sebeple kemik rezorbsiyonunu azaltması ve kontrol altına alınması gereken çoğu hastalıkta tercih edilmektedir. Kullanıma girdikleri 1969 yılından bu yana pek çok çalışma ile etkin, güvenilir ve iyi tolere edilebilir oldukları ortaya konmuştur. Oral bifosfonatlar genellikle osteopeni ve osteoporozda kullanılırken, inravenöz bifosfonatlar ilk olarak iskeletle ilişkili durumların düzeltilmesinde (kırıklar, kemik ağrısı, aşırı kemik rezorbsiyonu ile sonuçlanan hiperkalsemi durumlarında), multiple myelom, meme, prostat, akciğer ve kemik metaztazlı renal kanserler gibi malignitelerde kullanılmaktadır. Bifosfonatların yan etkileri minimal olarak bilinmektedir. Ancak ilacın uzun süreli kullanımına bağlı olarak bifosfonatın kemikte yüksek konsantrasyona ulaşması sonucunda, çenelerde osteonekrozlar ve oral mukoza epiteli üzerinde toksik etkiler gelişebilmektedir. Bu derlemede bifosfonatların kimyasal yapıları, etki mekanizmaları, endikasyonları, yan etkileri ve osteonekrozun tanı ve tedavisi hakkında önem arz eden bilgilerin verilmesi amaçlanmaktadır.

Anahtar Kelimeler

Bifosfonat, çene, kemik metabolizması, osteonekroz

Bisphosphonates and Osteonecrosis Seen in Jaws

Öz

Bisphosphonates are analogues of endogenous inorganic pyrophosphates that regulate stabilized bone mineralization. It is known that bisphosphonates reduce osteoclastic bone resorption by inactivating osteoclasts. For this reason, it is preferred in most diseases where bone resorption is to be reduced and controlled. Their use has been proven effective, reliable and well tolerated by many studies since 1969. Oral bisphosphonates are commonly used in osteopenia and osteoporosis, while intravenous bisphosphonates are first used in malignancies such as multiple myeloma, breast, prostate, lung, and bone metastases renal cancers, in the correction of skeletal related conditions (fractures, bone pain, hypercalcemia resulting in excessive bone resorption). Side effects of bisphosphonates are known to be minimal. However, due to the long-term use of the drug, the bisphosphonate can reach high concentrations in the bone, resulting in toxic effects on osteonecrosis and oral mucosal epidermis in the jaws. In this review, it is aimed to give important information about chemical structures, effect mechanisms, indications, side effects and diagnosis and treatment of osteonecrosis of bisphosphonates.

Anahtar Kelimeler

Bisphosphonate, jaw, bone metabolism, osteonecrosis

Kaynakça

• Luckman SP, Coxon FP, Ebetino FH, Russell RG, Rogers MJ. Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: evidence from structure-activity relationships in J774 macrophages. J Bone Mineral Research. 1998; 13(11): 1668-78.
• Torres SR, Chen CS, Leroux BG, Lee PP, Hollender LG, Lloid M, et al. Mandibular inferior cortical bone thickness on panoramic radiographs in patients using bisphosphonates. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015; 119(5): 584-92.
• Önal AG. Bifosfonatlar ve Diş Hekimliği Bitirme Tezi: Ege Üniversitesi 2013.
• Soydan S, Veziroğlu Şenel F, Araz K. Bifosfonata bağlı olarak çene kemiklerinde gelişen osteonekrozun patogenezi ve tedavisi. Hacettepe Diş Hekimliği Fakültesi Dergisi. 2009; 33(3): 61-8.
• Franchimont N, Canalis E. Management of glucocorticoid induced osteoporosis in premenopausal women with autoimmune disease. Autoimmunity Reviews. 2003; 2(4): 224-8.
• Katz H. Endodontic implications of bisphosphonate-associated osteonecrosis of the jaws: a report of three cases. Journal of Eendodontics. 2005; 31(11): 831-4.
• Miller PD. Bisphophonates: Pharmacology and use in the treatment of osteoporosis;. In: Marcus R FD, Nelson DA, Rosen CJ editor. San Diego USA: Elsevier American Pres. 2008; 1725-41.
• Sarıdoğan M, Gün K. Postmenopozal osteoporoz tedavisinde uzun dönem bifosfonat kullanımı ve görülebilen yan etkiler. Türkiye Osteoporoz Dünyasından.2010; 1(16): 66-71.
• Marx RE, Cillo JE, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. Journal of Oral and Maxillofacial Surgery. 2007; 65(12): 2397-410.
• Altay M. Bifosfonatlara bağlı gelişen çene osteonekrozlarının tedavisinde diyot lazerin destekleyici rolü. [Doktora Tezi]. Ankara: Hacettepe Dişhekimliği Fakültesi 2012.
• Senel FC, Tekin US, Durmus A, Bagis B. Severe osteomyelitis of the mandible associated with the use of non–nitrogen-containing bisphosphonate (disodium clodronate): report of a case. Journal of Oral and Maxillofacial Surgery. 2007; 65(3): 562-5.
• Cremers S, Papapoulos S. Pharmacology of bisphosphonates. Bone. 2011; 49(1): 42-9.
• Ruggiero SL, Woo SB. Biophosphonate-related osteonecrosis of the jaws. Dental Clinics of North America. 2008; 52(1): 111-28.
• Bartl R, Frisch B, von Tresckow E, Bartl C. Bisphosphonates in medical practice: actions-side effects-indications-strategies: Springer Science & Business Media; 2007.
• Crawford BS, McNulty RM, Kraut EH, Turowski RC. Extended use of intravenous bisphosphonate therapy for the prevention of skeletal complications in patients with cancer. Cancer Investigation. 2009; 27(10): 984-8.
• Shannon J, Shannon J, Modelevsky S, Grippo AA. Bisphosphonates and osteonecrosis of the jaw. Journal of the American Geriatrics Society. 2011; 59(12): 2350-5.
• Sarasquete ME, González M, San Miguel JF, García‐Sanz R. Bisphosphonate‐related osteonecrosis: Genetic and acquired risk factors. Oral Diseases. 2009; 15(6): 382-7.
• Kimmel D. Mechanism of action, pharmacokinetic and pharmacodynamic profile, and clinical applications of nitrogen-containing bisphosphonates. Journal of Dental Research. 2007; 86(11): 1022-33.
• Roelofs AJ, Thompson K, Gordon S, Rogers MJ. Molecular mechanisms of action of bisphosphonates: current status. Clinical Cancer Research. 2006; 12(20): 6222s-30s.
• Marx RE. Oral & Intravenous Bisphosphonate-Induced Osteonecrosis of the Jaws: History, Etiology, Prevention, and Treatment. Ann R Coll Surg Engl. 2009; 91: 446-50.
• Tuncer YH. Bifosfonat tedavisi gören hastaların osteonekroz gelişimi yönünden değerlendirilmesi ve serumdan kemik rezorbsiyon parametrelerinin ölçülmesi. [Doktora Tezi]: Hacettepe Üniversitesi Diş hekimliği Fakültesi 2011.
• Neville-Webbe HL, Gnant M, Coleman RE, editors. Potential anticancer properties of bisphosphonates. Seminars in Oncology; 2010: Elsevier.
• Mundy GR. Bisphosphonates as anticancer drugs. Expert opinion on investigational drugs. 1999; 8(12): 2009-15.
• Wood J, Bonjean K, Ruetz S, Bellahcène A, Devy L, Foidart JM, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. Journal of Pharmacology and Experimental Therapeutics. 2002; 302(3): 1055-61.
• Gnant M, Clézardin P. Direct and indirect anticancer activity of bisphosphonates: a brief review of published literature. Cancer Treatment Reviews. 2012; 38(5): 407-15.
• Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, et al. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Research. 2002; 62(22): 6538-44.
• Cheng A, Mavrokokki A, Carter G, Stein B, Fazzalari N, Wilson D, et al. The dental implications of bisphosphonates and bone disease. Australian Dental Journal. 2005; 50(s2): S4-S.
• Russell R, Rogers M. Bisphosphonates: from the laboratory to the clinic and back again. Bone. 1999; 25(1): 97-106.
• McLeod NM, Brennan PA, Ruggiero SL. Bisphosphonate osteonecrosis of the jaw: a historical and contemporary review. The Surgeon. 2012; 10(1): 36-42.
• Cryer B, Bauer DC, editors. Oral bisphosphonates and upper gastrointestinal tract problems: what is the evidence? Mayo Clinic Proceedings; 2002: Elsevier.
• Tanvetyanon T, Stiff P. Management of the adverse effects associated with intravenous bisphosphonates. Annals of Oncology. 2006; 17(6): 897-907.
• Önal L. Bifosfonat uygulanan ratlarda fibroblast büyüme faktörü'nün diş çekimi sonrası mukoza anjiogenezine etkisinin değerlendirilmesi [Doktora Tezi]: Süleyman Demirel Üniversitesi; 2013.
• Ruggiero SL, Mehrotra B. Bisphosphonate-related osteonecrosis of the jaw: diagnosis, prevention, and management. Annu Rev Med. 2009; 60: 85-96.
• Fedele S, Porter SR, D'Aiuto F, Aljohani S, Vescovi P, Manfredi M, et al. Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. The American Journal of Medicine. 2010; 123(11): 1060-4.
• Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. Journal of clinical Oncology. 2005; 23(34): 8580-7.
• Lehrer S, Montazem A, Ramanathan L, Pessin-Minsley M, Pfail J, Stock RG, et al. Bisphosphonate-induced osteonecrosis of the jaws, bone markers, and a hypothesized candidate gene. Journal of Oral and Maxillofacial Surgery. 2009; 67(1): 159-61.
• Sarasquete ME, García-Sanz R, Marín L, Alcoceba M, Chillón MC, Balanzategui A, et al. Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood. 2008; 112(7): 2709-12.
• Edwards BJ, Hellstein JW, Jacobsen PL, Kaltman S, Mariotti A, Migliorati CA. Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs. Journal of the American Dental Association (1939). 2008; 139(12): 1674-7.
• Reid IR, Bolland MJ, Grey AB. Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity?. Elsevier; 2007.
• Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws—2009 update. Journal of Oral and Maxillofacial Surgery. 2009; 67(5): 2-12.