BRZINA, UČINKOVITOST I SIGURNOST RISEDRONATA U LIJEČENJU OSTEOPOROZE

Zlatko Giljević, Tonko Vlak

Risedronate (Actonel 35 mg), which was promoted in Croatia a few months ago, is the latest (III) generation of bisphosphonates, the most efficient anti-resorption drugs that inhibit osteoclast-mediated bone resorption and change the bone metabolism. The effect of risedronate is 10 times stronger than that of alendronate, and 10.000 times stronger than that of etidronate. The bone turnover is reduced while the osteoblast activity and bone mineralisation are preserved. Decreases in biochemical markers of bone turnover were observed as soon as within 1 month and reached a maximum in 3-6 months of Actonel 35 mg application once a week or 5 mg a day. Several major international, randomised and placebo controlled clinical studies (VERT-NA, VERT-MN, HIP…) on more than 15,000 patients over 3-5 years of therapy have confi rmed the speed, efficacy and excellent tolerability of risedronate in treating postmenopausal and corticosteroid-induced osteoporosis. After only 6 months of treatment VERT-NA and VERT-MN have shown a significant reduction in vertebral fracture risk versus control group, radiographically by 62% and clinically by 69% in the fi rst year, which remains significant even after 5 years of treatment (50%) of postmenopausal osteoporosis. All the best properties of bisphosphonates have also been confirmed through a significant reduction in the relative risk of femoral neck fracture over 3 years of treatment by 40%, or by as much as 60% in female patients with osteoporosis and prevalent vertebral fracture, compared with controls. With risedronate we can achieve a quick and significant reduction in vertebral fracture risk in postmenopausal women (65%), especially among a high-risk population such as patients on long-term glucocorticoid therapy (70%) in the very first year of treatment. Prevention and treatment of glucocorticoid-induced osteoporosis is recommended in the administration of ≥7,5 mg of prednisone or prednisone equivalent in a duration longer than 3 months, irrespective of age or gender. Tolerability and safety of risedronate administration in osteoporosis is very good, almost the same as in the control group, although patients with earlier described or ongoing gastrointestinal troubles were also included. The incidence of endoscopically confirmed gastric ulcer in treatment with alendronate is significantly higher (13,2%) versus controls than in treatment with risedronate (4,1%). Risedronate is hence the first line of bisphosphonates for the reduction of vertebral and non-vertebral fracture risks in postmenopausal women with osteoporosis or those with a high risk of osteoporosis. It also efficiently prevents bone loss or improves bone density in men and women on a long-term corticosteroid therapy.

Risedronat (Actonel 35 mg), promoviran u Hrvatskoj prije nekoliko mjeseci, predstavlja zadnju (III) generaciju bisfosfonata, najučinkovitije antiresorptivne lijekove koji blokiraju osteoklastima induciranu razgradnju i mijenjaju metabolizam kosti. Učinak risedronata je 10 puta snažniji od učinka alendronata, a 10.000 puta snažniji od etidronata. Pregradnja kosti je smanjena dok su osteoblastička aktivnost i koštana mineralizacija očuvani. Smanjenje biokemijskih biljega pregradnje kosti nalazimo već unutar mjesec dana, s potpunim učinkom nakon 3-6 mjeseci primjene Actonela 35 mg jednom tjedno ili 5 mg dnevno. Nekoliko velikih međunarodnih, randomiziranih i placebo kontroliranih kliničkih studija (VERTNA, VERT-MN, HIP...) na više od 15.000 bolesnika tijekom 3-5 godina liječenja potvrdilo je brzinu, učinkovitost i izvrsnu podnošljivost risedronata u liječenju postmenopauzalne i kortikosteroidima uzrokovane osteoporoze. VERT-NA i VERT-MN su već nakon 6 mjeseci liječenja pokazale značajno smanjenje rizika prijeloma kralježaka prema kontrolnoj skupini, radiografski za 62% i klinički za 69% u prvoj godini, što ostaje značajno i nakon 5 godina liječenja (50%) u postmenopauzalnoj osteoporozi. Sve najbolje osobine bisfosfonata potvrđene su i značajnim smanjenjem relativnog rizika prijeloma vrata bedrene kosti tijekom 3 godine liječenja za 40%, odnosno u bolesnica s osteoporozom i prevalentnim prijelomom kralješka za čak 60% uspoređujući s kontrolnom skupinom. Pomoću risedronata postižemo brzo i značajno smanjenje rizika vertebralnih prijeloma u postmenopauzalnih žena (65%), osobito u visoko rizičnoj populaciji kao što su pacijenti na dugotrajnoj terapiji glukokortikoidima (70%) već tijekom prve godine liječenja. Prevencija i liječenje glukokortikoidima inducirane osteoporoze preporuča se kod primjene ≥7,5 mg prednisona ili ekvivalenta dulje od 3 mjeseca, bez obzira na dob ili spol. Podnošljivost i sigurnost primjene risedronata u osteoporozi vrlo je dobra, gotovo identična kao u kontrolnoj skupini iako su bili uključeni i pacijenti s ranije opisanim ili prisutnim gastrointestinalnim bolestima. Učestalost endoskopski potvrđenog vrijeda želuca je kod liječenja alendronatom značajno veća (13,2%) u odnosu na kontrolnu skupinu nego kod primjene risedronata (4,1%). Stoga je risedronat prva linija bisfosfonata za smanjenje rizika vertebralnih i nevertebralnih prijeloma u postmenopauzalnoj osteoporozi odnosno u onih s visokim rizikom za osteoporozu. Također uspješno prevenira gubitak ili popravlja gustoću kosti u muškaraca i žena koji su na dugotrajnoj kortikosteroidnoj terapiji.