Differences among bisfosfonates - specificity of risedronate (Actonel®)

Bisfosfonati, zlatni standard u terapijskim opcijama za liječenje osteoporoze, inhibiraju razgradnju kosti s relativno malo nuspojava. Rezultat je široka primjena u prevenciji i liječenju osteoporoze. Postoje jasne biokemijske i farmakološke razlike u skupini bisfosfonata. Risedronat se odlikuje relativno umjerenim afinitetom za hidroksiapatit i jakom inhibicijom ključnog enzima farnezil pirofosfat sintetaze (FPPS) u mevalonskom putu. Risedronat (Actonel®) prevenira vertebralne i nevertebralne prijeloma već nakon 6 mjeseci liječenja. Kliničkim ispitivanjima i opservacijskim ispitivanjima dokazano je smanjenje rizika od prijeloma kralježaka i smanjenje rizika od prijeloma kuka. Bolesnici su značajno češće izabirali lijek koji ima pouzdanije dokaze o antifrakturnoj učinkovitosti, u odnosu na način primjene.Bisphosphonates, a gold standard in therapeutic options for the management of osteoporosis, inhibit bone resorption with relatively few side effects. As a result, they are widely used for the prevention and treatment of osteoporosis. There are clear biochemical and pharmacological differences among bisfosfonates group. Risedronate has moderate mineral binding and has a higher inhibition of a key branch-point enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Risedronate (Actonel®) prevents vertebral and nonvertebral fractures as early as at 6 months of treatment. Clinical trials and observational trials have proved risk reduction of vertebral and hip fractures. Patients remarkably preferred therapy with a proven antifracture efficacy over a dosage frequency

Differences among bisfosfonates - specificity of risedronate (Actonel®)

Bisfosfonati, zlatni standard u terapijskim opcijama za liječenje osteoporoze, inhibiraju razgradnju kosti s relativno malo nuspojava. Rezultat je široka primjena u prevenciji i liječenju osteoporoze. Postoje jasne biokemijske i farmakološke razlike u skupini bisfosfonata. Risedronat se odlikuje relativno umjerenim afinitetom za hidroksiapatit i jakom inhibicijom ključnog enzima farnezil pirofosfat sintetaze (FPPS) u mevalonskom putu. Risedronat (Actonel®) prevenira vertebralne i nevertebralne prijeloma već nakon 6 mjeseci liječenja. Kliničkim ispitivanjima i opservacijskim ispitivanjima dokazano je smanjenje rizika od prijeloma kralježaka i smanjenje rizika od prijeloma kuka. Bolesnici su značajno češće izabirali lijek koji ima pouzdanije dokaze o antifrakturnoj učinkovitosti, u odnosu na način primjene.Bisphosphonates, a gold standard in therapeutic options for the management of osteoporosis, inhibit bone resorption with relatively few side effects. As a result, they are widely used for the prevention and treatment of osteoporosis. There are clear biochemical and pharmacological differences among bisfosfonates group. Risedronate has moderate mineral binding and has a higher inhibition of a key branch-point enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Risedronate (Actonel®) prevents vertebral and nonvertebral fractures as early as at 6 months of treatment. Clinical trials and observational trials have proved risk reduction of vertebral and hip fractures. Patients remarkably preferred therapy with a proven antifracture efficacy over a dosage frequency

Treatment of osteoporosis by risedronate - speed, efficacy and safety

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 (VERT-NA, 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.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 confirmed 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 first 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

Da li je znanje pacijenata o osteoporozi povezano s unosom kalcija?

The aim of the study was to determine if calcium intake in patients with osteoporosis and osteopenia is influenced by the patient’s knowledge about the disease. The results presented are collected from an ongoing survey on dietary and other behaviour in women with lower bone density. Subjects were 197 women with an average age of 62.9 years. Specially designed quantified Food Frequency Questionnaire (FFQ) and, additional questionnaire for demographic data were used. When asked in what period of life they consumed the highest quantity of milk and dairy products, in the highest percent of subjects (27.8%) the answer was after the age of 50 years. In this case, although not significantly, the ages are negatively correlated with calcium intake. Years of education did not significantly correlate with calcium intake. Subjects that knew the recommended calcium intake in average had also a higher calcium intake (1369.6 mg) than those who did not (929.2 mg) and had significantly higher (p = 0.01) supplemental calcium intake than those who did not know the recommended calcium intake. No significant difference in calcium intake was observed when osteoporosis, reported in family anamnesis, is taken into account. The period of time from diagnosis did not correlate with calcium intake. Significant correlation (p < 0.01) was observed for calcium intake as well as the number of correct answers on questions about osteoporosis and food checklist where benefits of calcium sources are recognize. This study showed that a patient’s knowledge about osteoporosis is important in achieving adequate calcium intake.Cilj ovog istraživanja bio je utvrditi da li je unos kalcija u pacijenata s osteoporozom i osteopenijom povezan sa znanjem o bolesti. Prikazani su dosad prikupljeni rezultati istraživanja o prehrambenim i drugim navikama u žena niske mineralne gustoće kosti. Ispitanici su bile 197 žena prosječne dobi 62,9 godina. Upotrijebljen je posebno napravljen upitnik o učestalosti konzumiranja hrane i pića (FFQ), te dodatan upitnik za demografske podatke. Na pitanje u kojem periodu života su konzumirali najveće količine mlijeka i mliječnih proizvoda, najveći postotak ispitanika (27,8%) je odgovorio nakon 50. godine života, ali utvrđena je negativna, iako ne i statistički značajna korelacija između dobi i unosa kalcija. Godine obrazovanja nisu statistički značajno korelirale s unosom kalcija. Ispitanici koji su znali koja je preporuka za unos kalcija su imali veći prosječan unos (1369,6 mg vs. 929,2 mg) i imali su statistički značajno veći unos kalcija dodatcima prehrani nego oni koji nisu znali preporuku (p = 0,01). Nije utvrđena značajna razlika unosa kalcija s obzirom na to da li u obitelji ima ili je bilo oboljelih od osteoporoze. Period koji je protekao od dijagnoze osteoporoze nije koreliralo s unosom kalcija. Statistički značajna korelacija (p < 0,01) je utvrđena za unos kalcija i broj točnih odgovora na pitanja o osteoporozi i prepoznavanju dobrih izvora kalcija. Ovo istraživanje je pokazalo da je znanje o osteoporozi u oboljelih značajno u postizanju adekvatnog unosa

Treatment of Osteoporosis

Osteoporoza je jedna od najčešćih metaboličkih bolesti i zahvaća 8 % do 10 % stanovništva. Budući da je prijelom najteža posljedica osteoporoze, vrlo je važno otkriti bolesnike koji imaju rizik nastanka prijeloma, dati im farmakološku terapiju i savjetovati im promjenu načina života. Nekoliko je lijekova pokazalo sposobnost smanjenja broja prijeloma kralježnice i/ili perifernog skeleta u bolesnika s osteoporozom. Antiresorptivni su lijekovi temelj terapije, ali su i anabolički lijekovi odnedavno proširili mogućnosti liječenja. Antiresorptivni lijekovi, estrogeni, selektivni modulatori estrogenskih receptora, bisfosfonati i kalcitonin, djeluju tako da smanjuju koštanu pregradnju. Paratireoidni hormon potiče novo stvaranje kosti popravljajući arhitekturu i gustoću kosti. Stroncijev ranelat smanjuje rizik osteoporotičnih prijeloma djelujući na oboje - smanjenje razgradnje i povećanje izgradnje kosti. Druga potencijalna liječenja osteoporoze također su opisana u ovome članku.Osteoporosis is among the most frequent metabolic diseases affecting 8 % to 10 % of the population. Since the most disturbing outcome of osteoporosis is a fracture, it is important to identify patients at risk and intervene with pharmacologic therapies and lifestyle changes. Several drugs have shown their ability to reduce vertebral and/or peripheral fractures in patients with osteoporosis. Antiresorptive agents are a basis of therapy, but anabolic drugs have recently widened therapeutic options. Antiresorptive medications, estrogens, selective estrogen receptor modulators, bisphosphonates and calcitonins, work by reducing the rates of bone remodeling. Parathyroid hormone stimulates new bone formation, repairing architectural defects and improving bone density. Strontium ranelate reduces the risk for osteoporotic fractures by both inhibiting bone resorption and increasing bone formation. Other potential therapies for osteoporosis are also reviewed in this article

Diet Quality in Elderly Nursing Home Residents Evaluated by Diet Quality Index Revised (DQI-R)

The objective of this research was to evaluate diet quality in elderly nursing home residents and to point out the critical dietary components. The participants (277 females and 62 males) were recruited from all elderly nursing homes in Zagreb and each of elderly nursing homes was equally represented in this study. The age of subjects was ranging from 61 to 93 years; most of the females (53.4%) and males (53.2%) were between 70 and 80 years old. The dietary data from the multi pass 24-hour recall were used to compute the Diet Quality Index Revised (DQI-R). DQI-R is an instrument that provides a summary assessment of a diet’s overall healthfulness and is based on ten different aspects, including recommendations for both nutrient and food types. Pearson correlation analysis was used to compare the total DQI-R score with dietetic parameters and t-test was calculated between mean values of all the components of DQI-R as well as for total DQI-R score for men and women. The mean DQI-R score for the 339 sample was 62.1±11.7. The biggest number of participants satisfied recommendations about dietary cholesterol intake (88.5 % of participants) and dietary moderation score (71.1% of participants) but nobody satisfied recommendation about dietary diversity score. Only 3.2% of subjects had an adequate calcium intake (6.5% of male participants and only 2.5% of female participants). Recommended servings of fruit intake were satisfied by 19.8% of population, 30.4% satisfied vegetables recommendations and 38.6% recommendations for grains. According to DQI-R, beside positive dietary habits regarding dietary moderation and dietary cholesterol intake the population of elderly nursing home residents in the capital of Croatia needs improvement in other dietary habits in order to enhance successful aging

The role of IGF-1 (CA)n polymorphism on peak bone mass attainment in males

Cilj: Idiopatska osteoporoza u muškaraca prvenstveno je posljedica niske vršne koštane mase koja je genetski uvjetovana. S obzirom na njegovu važnu ulogu u metabolizmu kosti, između brojnih gena kandidata u patogenezi osteoporoze, od posebnog je interesa gen za čimbenik rasta sličan inzulinu (IGF-1). Prethodna istraživanja pokazala su da je polimorfizam mikrosatelitne regije citozin-adenin (CA)n unutar gena za IGF-1 povezan sa serumskom koncentracijom IGF-I, stoga je primarni cilj ovog istraživanja bio analizirati utjecaj ovog polimorfizma na vršnu koštanu masu u muškaraca. Metode: U istraživanje su uključena 92 zdrava muškarca u dobi od 21 do 35 godina. Svakom je ispitaniku izmjerena mineralna gustoća kosti (BMD) u lumbalnoj kralježnici i proksimalnom dijelu bedrene kosti, koncentracije biljega koštane pregradnje, 25-OHD i spolnih hormona. Rezultati: Ispitanici u kojih je nađen alel (CA)18 (genotip 18+) imali su niži BMD u svim mjerenim područjima, no razlike između ispitivanih skupina nisu bile statistički značajne. Ipak, u homozigota (CA)18 nađen je značajno niži BMD u području vrata bedrene kosti (P=0,03), trohantera (P=0,01) i proksimalnog dijela bedrene kosti (P=0,04), dok razlike u koncentracijama biljega koštane pregradnje, 25-OHD, slobodnog testosterona i estradiola nisu bile statistički značajne. Rasprava: Rezultati ovog istraživanja ukazali su na mogući negativan utjecaj alela IGF-1 (CA)18 na vršnu koštanu masu u muškaraca. Ipak, za definitivne zaključke o ulozi tog polimorfizma u patogenezi osteoporoze potrebna su daljnja istraživanja na većem broju ispitanika i u različitim populacijama.Aim: Idiopathic osteoporosis in males is influenced predominantly by low peak bone mass as a feature under a strong genetic control. Among number of candidate genes, IGF-1 gene is of particular interest due to its important role in bone metabolism. It has been reported that IGF-1 citozin-adenin (CA)n polymorphism is related to serum IGF-1 concentration. Therefore, in the present study we examined the influence of certain IGF-1 (CA)n alleles on peak bone mass attainment in males. Methods: Study sample consisted of 92 unrelated healthy male volunteers, aged 21-35. In each subject, lumba spine and proximal femur bone mineral density (BMD), bone turnover markers, 25-OHD and sex hormones levels were measured. Results: IGF-1 (CA)18 allele (genotype 18+) were found to be �associated with low-lower BMD in all measured areas but the differences between analysed groups were not significant. However, homozygotes (CA)18 had significantly lower femoral neck (P=0,03), trochanter (P=0,01) and total hip (P=0,04) BMD whereas differences in bone turnover markers, 25-OHD, free testosterone and estradiol concentrations were not significant. Discussion: The results of the present study suggested possible negative effect of the IGF-1 (CA)18 allele on the peak bone mass attainment in males. However, for definitive conclusion about the role of this polymorphism in the pathogenesis of osteoporosis further studies in different populations and with larger number of participants are needed

The role of IGF-1 (CA)n polymorphism on peak bone mass attainment in males

Cilj: Idiopatska osteoporoza u muškaraca prvenstveno je posljedica niske vršne koštane mase koja je genetski uvjetovana. S obzirom na njegovu važnu ulogu u metabolizmu kosti, između brojnih gena kandidata u patogenezi osteoporoze, od posebnog je interesa gen za čimbenik rasta sličan inzulinu (IGF-1). Prethodna istraživanja pokazala su da je polimorfizam mikrosatelitne regije citozin-adenin (CA)n unutar gena za IGF-1 povezan sa serumskom koncentracijom IGF-I, stoga je primarni cilj ovog istraživanja bio analizirati utjecaj ovog polimorfizma na vršnu koštanu masu u muškaraca. Metode: U istraživanje su uključena 92 zdrava muškarca u dobi od 21 do 35 godina. Svakom je ispitaniku izmjerena mineralna gustoća kosti (BMD) u lumbalnoj kralježnici i proksimalnom dijelu bedrene kosti, koncentracije biljega koštane pregradnje, 25-OHD i spolnih hormona. Rezultati: Ispitanici u kojih je nađen alel (CA)18 (genotip 18+) imali su niži BMD u svim mjerenim područjima, no razlike između ispitivanih skupina nisu bile statistički značajne. Ipak, u homozigota (CA)18 nađen je značajno niži BMD u području vrata bedrene kosti (P=0,03), trohantera (P=0,01) i proksimalnog dijela bedrene kosti (P=0,04), dok razlike u koncentracijama biljega koštane pregradnje, 25-OHD, slobodnog testosterona i estradiola nisu bile statistički značajne. Rasprava: Rezultati ovog istraživanja ukazali su na mogući negativan utjecaj alela IGF-1 (CA)18 na vršnu koštanu masu u muškaraca. Ipak, za definitivne zaključke o ulozi tog polimorfizma u patogenezi osteoporoze potrebna su daljnja istraživanja na većem broju ispitanika i u različitim populacijama.Aim: Idiopathic osteoporosis in males is influenced predominantly by low peak bone mass as a feature under a strong genetic control. Among number of candidate genes, IGF-1 gene is of particular interest due to its important role in bone metabolism. It has been reported that IGF-1 citozin-adenin (CA)n polymorphism is related to serum IGF-1 concentration. Therefore, in the present study we examined the influence of certain IGF-1 (CA)n alleles on peak bone mass attainment in males. Methods: Study sample consisted of 92 unrelated healthy male volunteers, aged 21-35. In each subject, lumba spine and proximal femur bone mineral density (BMD), bone turnover markers, 25-OHD and sex hormones levels were measured. Results: IGF-1 (CA)18 allele (genotype 18+) were found to be �associated with low-lower BMD in all measured areas but the differences between analysed groups were not significant. However, homozygotes (CA)18 had significantly lower femoral neck (P=0,03), trochanter (P=0,01) and total hip (P=0,04) BMD whereas differences in bone turnover markers, 25-OHD, free testosterone and estradiol concentrations were not significant. Discussion: The results of the present study suggested possible negative effect of the IGF-1 (CA)18 allele on the peak bone mass attainment in males. However, for definitive conclusion about the role of this polymorphism in the pathogenesis of osteoporosis further studies in different populations and with larger number of participants are needed

Smjernice za prevenciju, prepoznavanje i liječenje nedostatka vitamina D u odraslih [Guidelines for the prevention, detection and therapy of vitamin D deficiency in adults]

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin D