Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis.

UNLABELLED: In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. INTRODUCTION: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. METHODS: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm. RESULTS: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. CONCLUSIONS: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate.

Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis.

SUMMARY: Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. CONCLUSION: In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.

Strontium ranelate prevents quality of life impairment in post-menopausal women with established vertebral osteoporosis.

UNLABELLED: Strontium ranelate reduces the risk of fracture in post-menopausal osteoporotic women with prevalent fractures for whom quality of life is severely impaired. The SOTI study, which used the SF-36 questionnaire and disease-specific QUALIOST module, demonstrated that treatment with strontium ranelate improved osteoporotic women's quality of life compared with placebo. INTRODUCTION: The Spinal Osteoporosis Therapeutic Intervention (SOTI) study demonstrated the effect of orally administered strontium ranelate versus placebo on the incidence of new vertebral fractures and compared impact on quality of life (QoL). METHODS: QoL was assessed 6 monthly over 3 years using the QUALIOST and SF-36 questionnaires in post-menopausal osteoporotic women with prevalent fracture taking strontium ranelate or placebo 2 g/day. A total of 1,240 women were included (strontium ranelate: n=618 and placebo: n=622). RESULTS: The QUALIOST total score decreased in the strontium ranelate group, indicating preserved QoL compared with a deterioration in the placebo group (P=0.016). Strontium ranelate patients had reduced QUALIOST emotional and physical dimension scores (P=0.019 and 0.032, respectively, versus placebo), indicating beneficial effects on emotional and physical functioning. There was a trend towards better SF-36 scores in the strontium ranelate group, although there were no significant between-group differences. More strontium ranelate patients (+31%) were free from back pain over 3 years versus placebo (P=0.005), with a significant effect from the first year of treatment (P=0.023). CONCLUSION: Strontium ranelate has beneficial effects on QoL in women with post-menopausal osteoporosis compared with placebo.

Relationship between change in femoral neck bone mineral density and hip fracture incidence during treatment with strontium ranelate.

OBJECTIVE: Strontium ranelate (SR) increases bone mineral density (BMD) in postmenopausal osteoporotic women and reduces vertebral and non-vertebral fracture incidence. Hip fracture reduction has also been observed during 3-year treatment with SR in osteoporotic women at high risk of hip fracture. The objective of this study is to analyse the association between BMD changes and hip fracture incidence during treatment with SR. MATERIAL AND METHODS: In this post-hoc analysis, 465 women aged over 74 years with low BMD at the femoral neck (T-score < or = -2.4 according to NHANES normative values) were selected from the population of a recently published study (the Treatment of Peripheral Osteoporosis Study - TROPOS). BMD was assessed at the femoral neck at baseline and after a follow-up of 3 years. Hip fractures were reported by study investigators. RESULTS: After adjusting for age, body mass index, femoral neck BMD at baseline and number of prevalent vertebral fractures, we found that for each 1% increase in femoral neck BMD observed after 3 years, the risk to experience a hip fracture after 3 years decreased by 7% (95% CI: 1-14%) (p = 0.04). In patients experiencing a hip fracture over 3 years of treatment with SR, femoral neck BMD increased by (mean [SE]) 3.41 (1.02)% compared to 7.23 (0.81)% in patients without hip fracture (p = 0.02). CONCLUSION: In this post-hoc analysis of women undergoing 3 years of SR treatment, an increase in femoral neck BMD is associated with a decrease in hip fracture incidence.

[Comparative analysis of three treatment regimens for treating gonarthritis with calcitonin, naproxen and flavonoids based on EULAR criteria and visual analogue scale (VAS)]. / Porównawcza analiza trzech schematów leczenia gonarthritis kalcytonina, naprowenem i flaksonoidami w oparciu o kryteria EULAR i wizualna skale analogowa bólu (VAS).

UNLABELLED: The newest laboratory and clinical elaborations have described a stimulatory effect of salmon calcitonin (sCT) on cultivated chondrocytes and cartilage explants in regard to their secretory function of glycosaminoglycans, collagen t. II and hyaluonic acid as well as have shown anticatabolic effect of sCT on numerous animal models of osteoarthropathy. Moreover, very few clinical indicated profitable effect of CT on degenerative joint diseases and on rheumatoid arthritis. The aim of the present study is to compare the curative effect of sCT (Miacalcic, Sandoz, nasal spray, 2 x 100 IU/day ) vs flavonoides (VR, Venoruton, Zyma, 2 x 0.6 + Vit. C. 0.2/day) with or without naproxen sodium (AP, Apranax, 2 x 0.550/day) in 30 patients suffering from gonarthritis, treated in 10 months in one of the three regimes: I--(n = 10, BMI-33.3, aged 59.5 y., Larsen gr. -2.5): 1st month-VR, 2 and 3-sCT, 4 and 5-VR, 6 and 7-AP, 8.9 and 10-VR; II--(n = 10, BMI-28.8, aged 56 y., Larsen gr. 2.95): 1st m.-VR, 2 and 3-Ap, 4 and 5-VR, 6 and 7-sCT, 9.9 and 10-VR; III--(n = 10, BMI-31.4, aged 58 y., Larsen gr.-2.8): 1st m.-VR, 2 and 3-sCT, 4 and 5-VR, 6 and 7-sCT, 8.9 and 10-VR. Clinical effects of treatment were evaluated by EULAR criteria, VAS, and the paracetamol consumption. RESULTS: The best results according to all three criteria of improvement have been observed in group III treated only with sCT and VR followed by group I in which sCT was given as the first active drug. This effect lasted until three months after the withdrawal of sCT and/or naproxen. This results supported our opinion on antiosteoarthritic ability of salmon calcitonin and marked curative effect of flavonoides in the treatment of osteoarthritis.

[Bone density in axial and peripheral skeleton and mineral density of the entire body as an age dependent factor in a population sample of healthy women]. / Gestosc masy kostnej w szkielecie osiowym i obwodowym oraz gestosc mineralna calego ciala w zaleznosci od wieku w próbce populacyjnej zdrowych kobiet.

Bone mineral density has been measured with dual energy X-ray absorptiometry (DEXA) in both axial and peripheral skeleton of 208 randomly selected healthy women aged between 20 and 80 years. Examined women have been stratified into the age groups of every 10 years. Bone mineral density has been measured in lumbar spine L2-L4 (AP), L2-L3 (Lat.) and proximal femur together with total body mineral density in every examined woman. The obtained results are considered reference values for the Polish population.

[Calcitonin in treating bone and joint lesions--clinical and experimental findings and personal experience]. / Kalcytonina w leczeniu zmian kosci i stawów--uzasadnienia doswiadczalne i kliniczne oraz doswiadczenia wlasne.

Several experimental studies in the animal models and the use of calcitonin in patients with osteoarthritis, rheumatoid arthritis, and osteoporosis have shown multiple actions of this hormone, justifying its use in the wide range of osteoarthritic pathologies. We used well known animal models of tests to study chondro-tropic drugs such as: post-corticoid arthropathy, partial meniscectomy, immobilization of the lower extremity of rabbits, follow-up of the natural knee degeneration in the black mouse C57, and radiolabelled sulphates uptake by the cartilage, and have shown: (a) anticatabolic effect of salmon calcitonin as measured as GAG levels, width of articular space, and histochemical and morphologic examination of the cartilage in some model arthropathies, (b) anti-osteoporotic properties counteracting an effect of corticosteroids, (c) increased uptake of sulphates by the articular cartilage of the rat following calcitonin administration in vivo. The studies explaining mechanisms of calcitonin actions included IGF-1 assays and beta-endorphins. The former increased transiently after calcitonin administration whereas the latter increased after non-steroid anti-inflammatory agents use. Calcitonin decreased gastrin secretion with negligible effect on calcium ions and prostaglandin E2 levels in blood plasma while it potently acid secretion and increasing gastric mucus content in the stomach. The use of calcitonin in patients with arthrosis, rheumatoid arthritis, and osteoporosis with accompanying peptic and/or duodenal ulcers produced healing of peptic and/or duodenal ulcers in 75% of patients within 4 weeks with simultaneous shortening of the morning stiffness, increase in hand grip strength (in rheumatoid arthritis), and significant decrease in pain as well as an improvement in the quality of life in the majority of the treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Chondroprotective action of salmon calcitonin in experimental arthropathies.

To assess whether calcitonin exerts an influence on cartilage, three models of arthropathies in rabbits--representing three different modes of cartilage destruction--were used: (1) corticosteroid administration (endocrinological disturbances model); (2) meniscectomy (mechanical stress model); and (3) immobilization of the hind leg (nutritional disorder model). After 12 weeks of methylprednisolone (MP) administration, the rabbit femur heads displayed cartilage erosions, marked decrease of glycosaminoglycans (GAG) content, and narrowing of joint spaces. Elevation of serum uronic acid, activity of alkaline phosphatase, and calmodulin content was evident. All these changes were minimal--close to normal--in the group treated for 12 weeks with MP + salmon calcitonin (sCT). Partial meniscectomy and hind leg immobilization caused statistically significant loss of GAG from the cartilage and narrowing of the knee joint space during the same experimental period, 12 weeks. In both these models the groups of rabbits treated simultaneously with sCT showed only insignificantly smaller joint spaces and GAG content. These results support our hypothesis of a chondroprotective property of calcitonin. However, the mechanism through which calcitonin influences joint cartilage remains unknown. A direct effect of calcitonin on cultivated chondrocytes, as well as the role of calmodulin, beta-endorphins, calcium, and interleukin-1 in the process are discussed.

Calcitonin versus cimetidine or De-Nol in gastric ulcer treatment. An endoscopically controlled trial.

110 patients with benign gastric ulcer and concomitant joint diseases (rheumatoid arthritis, osteoarthrosis) were treated in a comparative short-term clinical trial to assess the relative efficacy of calcitonin (daily 100 MRC of salmon calcitonin intramuscularly), cimetidine (daily 1000 mg orally) and colloidal bismuth subcitrate (De-Nol-four times a day in doses of 5 ml diluted with 15 ml of water). Groups of patients were comparable according to age, sex, duration of ulcer disease, smoking habits, gastric acid secretion and mean ulcer size. The ulcer healing was controlled endoscopically after 2 and 4 weeks of the treatment. There was no significant difference in the ulcer healing rate between three groups neither after 2 weeks (calcitonin-36.7% of healed ulcers, cimetidine-37.5% and De-Nol-35.0% nor after 4 weeks respectively (76.7%, 72.5% and 77.5%). In the calcitonin group a gradual joint pain relief was observed in 84% of patients who complained arthralgia. The moderate side effects (headache, nausea, flush) were observed only in the patients treated with calcitonin (8 subjects). We suggest that calcitonin may be considered as a valid anti-ulcer drug in the peptic ulcer patients with concomitant rheumatological diseases especially with osteoporosis.

[Secretion of gastric mucus following maximal pentagastrin stimulation]. / Die Sekretion des Magenschleims nach einem maximalen Pentagastrinreiz.

The aim of the thesis was the observation of the gastric mucus secretion on the basis of carbohydrate components and protein secretion into the gastric lumen. 15 healthy volunteers were investigated: 7 males and 8 females aged 20-37 (average rate 27). In this group gastric juice was aspirated after administration of single 6 micrograms/kg BW stimulus of pentagastrin. Concentration and output of hydrochloric acid, pepsin, protein and carbohydrate components of gastric juice fucose, sialic acid, hexosamines and hexoses were measured. Carbohydrate components and proteins included informations concerning gastric mucus secretion into gastric lumen. It was shown that the highest gastric mucus secretion occurred before maximal gastric acid secretion. This is of importance for keeping balance between so called aggressive and protective mechanisms. It is of great importance in pathophysiology of stomach.