The Experts below are selected from a list of 189 Experts worldwide ranked by ideXlab platform
Yasuo Ohashi - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of monthly oral minodronate in patients with Involutional Osteoporosis
Osteoporosis International, 2012Co-Authors: Ryo Okazaki, Masao Fukunaga, Masataka Shiraki, Hiroshi Hagino, Toshitaka Nakamura, Teruki Sone, Masako Ito, Hideki Mizunuma, Yoshiki Nishizawa, Yasuo OhashiAbstract:Summary Monthly minodronate at 30 or 50 mg had similar efficacy as 1 mg daily in terms of change in bone mineral density (BMD) and bone turnover markers with similar safety profiles. This new regimen provides patients with a new option for taking minodronate.
-
efficacy and tolerability of once weekly administration of 17 5 mg risedronate in japanese patients with Involutional Osteoporosis a comparison with 2 5 mg once daily dosage regimen
Journal of Bone and Mineral Metabolism, 2006Co-Authors: Hideaki Kishimoto, Kazuhiro Kushida, Masao Fukunaga, Masataka Shiraki, Akira Itabashi, Hajime Nawata, Toshitaka Nakamura, Hiroaki Ohta, Kunio Takaoka, Yasuo OhashiAbstract:In this multicenter, randomized, double-blind controlled trial, the efficacy and safety of once-weekly dosing with 17.5 mg risedronate was compared with once-daily dosing with 2.5 mg risedronate in Japanese patients with Involutional Osteoporosis. A total of 496 patients were randomized to receive either once-weekly (n = 249) or once-daily (n = 247) treatment. All patients were supplemented with 200 mg/day calcium. Following 48 weeks of treatment, the mean (±SD) percent changes, from baseline, in the bone mineral density of the lumbar spine (L2-L4 BMD) in the once-weekly and once-daily treatment groups were 5.36 ± 4.27% and 5.87 ± 4.47%, respectively. The difference between the groups was −0.5% (95% confidence interval: −1.35% to 0.35%), demonstrating that the effect on BMD of once-weekly treatment was not inferior to that of once-daily treatment. The time-course reductions in biochemical markers of bone resorption (urinary N- and C-telopeptide of type I collagen) and bone formation (bone-specific alkaline phosphatase) were similar for the two dosing regimens. There were no differences in the incidence of new vertebral fractures or the worsening of existing fractures between the once-weekly (2.2%) and once-daily (2.7%) dosing regimens. No significant differences were observed between the two dosing regimens in the incidence or the type of adverse events. However, 10.1% of the patients in the once-daily group withdrew due to adverse events as compared to 5.2% in the once-weekly group. Moreover, drug-related adverse events, including upper gastrointestinal disorders and abnormal changes in laboratory parameters, tended to be less in the once-weekly dosing regimen than in the once-daily dosing regimen. In conclusion, once-weekly oral dosing with 17.5 mg risedronate was well tolerated in Japanese osteoporotic patients, and showed equivalent efficacy to once-daily oral dosing with 2.5 mg risedronate. This once-weekly regimen is expected to provide a more convenient therapeutic option as an alternative to daily dosing and to enhance patient compliance in long-term therapy for Osteoporosis.
Hideaki Kishimoto - One of the best experts on this subject based on the ideXlab platform.
-
Phase II/III, randomized, double-blind, parallel-group study of monthly delayed-release versus daily immediate-release risedronate tablets in Japanese patients with Involutional Osteoporosis
Journal of Bone and Mineral Metabolism, 2020Co-Authors: Satoshi Soen, Hideaki Kishimoto, Hiroshi Hagino, Hiroaki Ohishi, Teruki Sone, Tsukasa Fujimoto, Emma Sasaki, Sakae Tanaka, Toshitsugu SugimotoAbstract:Absorption of oral immediate-release (IR) risedronate tablets is reduced by food intake, thus a delayed-release (DR) tablet has been developed to overcome the necessity of taking IR tablets under fasting conditions. This randomized, double-blind, phase II/III study compared efficacy and safety of risedronate IR once-daily (QD) and DR once-monthly (QM) tablets in Japanese patients with Involutional Osteoporosis. Patients received 2.5 mg IR on awakening QD, or 25 or 37.5 mg DR on awakening, following breakfast, or 30 min after breakfast, QM for 12 months. Primary endpoint was non-inferiority in mean percent change from baseline to end of study (month 12, last observation carried forward [M12, LOCF]) in mean lumbar spine (L_2–L_4) bone mineral density (BMD) between risedronate IR on awakening and DR following breakfast. Mean percent changes in (L_2–L_4) BMD at M12, LOCF were 5.07% (IR at awakening, n = 190), 3.36% (25 mg DR following breakfast, n = 194), and 4.11% (37.5 mg DR following breakfast, n = 181). Mean percent change in (L_2–L_4) BMD was numerically lower in the DR following breakfast groups versus the respective on awakening and 30 min after breakfast DR groups. Overall incidences of treatment-emergent adverse events (TEAEs) were comparable between groups. In the DR groups, 1.5–4.0% of patients reported TEAEs potentially associated with acute-phase reactions versus 0% in the IR group. In this study, non-inferiority could not be declared for 37.5 or 25 mg DR following breakfast QM ( p = 0.1346 or p = 0.6711, respectively) versus 2.5 mg IR on awakening QD.
-
efficacy tolerability and safety of once monthly administration of 75mg risedronate in japanese patients with Involutional Osteoporosis a comparison with a 2 5mg once daily dosage regimen
Bone, 2014Co-Authors: Hiroshi Hagino, Hideaki Kishimoto, Hiroaki Ohishi, Sayako Horii, Toshitaka NakamuraAbstract:Oral risedronate has been shown to be effective in the treatment of Osteoporosis when administered once-daily or once-weekly in Japan. This randomized, double-blind, multicenter 12-month study was conducted to compare the efficacy and tolerability of oral risedronate 75mg once-monthly with 2.5mg once-daily in Japanese patients with Involutional Osteoporosis. Bone mineral density (BMD), biochemical markers of bone metabolism, fractures, and adverse events (AEs) were evaluated. At the end of the study (Month 12, last observation carried forward [M12, LOCF]), mean percent change (SD) from baseline in lumbar spine (L2-L4) BMD, measured by dual energy X-ray absorptiometry (primary endpoint), was increased by 5.69 (4.00)% in the 2.5mg once-daily group (n=428), and 5.98 (4.54)% in the 75mg once-monthly group (n=422). In the non-inferiority t-test (non-inferiority margin Δ=1.5%), the 75mg once-monthly group was non-inferior to the 2.5mg once-daily group (p<0.0001). The difference between treatment groups was 0.28% (95% CI, -0.31% to 0.88%). Changes in biochemical markers of bone metabolism were generally comparable in the two groups, although decreases in the percent change from baseline in urinary NTX/CRN and CTX/CRN were statistically greater in the 2.5mg once-daily group than the 75mg once-monthly group. The frequency of new vertebral fractures (including aggravation of prevalent fractures) at the end of the study (M12, LOCF) was also similar in the two groups: 1.2% in the 2.5mg once-daily group and 1.3% in the 75mg once-monthly group. The incidence of mild/moderate/severe AEs was 75.5%/6.3%/0.5% in the 2.5mg once-daily group and 77.7%/8.1%/0.7% in the 75mg once-monthly group. AEs associated with gastrointestinal symptoms occurred in approximately 30% of subjects in each group but with no severe cases. AEs potentially associated with acute phase reaction (including symptoms of influenza-like illness or pyrexia starting within 3days of the first dose of the study drug and with a duration of 7days or less) only occurred in the 75mg once-monthly group (2.1%, 9/422 subjects; influenza-like symptoms in 1 subject and pyrexia in 8 subjects), although the incidence was low without any severe cases. In conclusion, risedronate 75mg once-monthly (a dosage which is 30 times higher than risedronate 2.5mg once-daily) had non-inferior efficacy in terms of BMD and was similarly well tolerated compared to the once-daily regimen in Japanese patients with Involutional Osteoporosis. Consistent with the once-daily and once-weekly dosage, the once-monthly dosage of risedronate 75mg was half that used outside Japan (150mg).
-
efficacy and tolerability of once weekly administration of 17 5 mg risedronate in japanese patients with Involutional Osteoporosis a comparison with 2 5 mg once daily dosage regimen
Journal of Bone and Mineral Metabolism, 2006Co-Authors: Hideaki Kishimoto, Kazuhiro Kushida, Masao Fukunaga, Masataka Shiraki, Akira Itabashi, Hajime Nawata, Toshitaka Nakamura, Hiroaki Ohta, Kunio Takaoka, Yasuo OhashiAbstract:In this multicenter, randomized, double-blind controlled trial, the efficacy and safety of once-weekly dosing with 17.5 mg risedronate was compared with once-daily dosing with 2.5 mg risedronate in Japanese patients with Involutional Osteoporosis. A total of 496 patients were randomized to receive either once-weekly (n = 249) or once-daily (n = 247) treatment. All patients were supplemented with 200 mg/day calcium. Following 48 weeks of treatment, the mean (±SD) percent changes, from baseline, in the bone mineral density of the lumbar spine (L2-L4 BMD) in the once-weekly and once-daily treatment groups were 5.36 ± 4.27% and 5.87 ± 4.47%, respectively. The difference between the groups was −0.5% (95% confidence interval: −1.35% to 0.35%), demonstrating that the effect on BMD of once-weekly treatment was not inferior to that of once-daily treatment. The time-course reductions in biochemical markers of bone resorption (urinary N- and C-telopeptide of type I collagen) and bone formation (bone-specific alkaline phosphatase) were similar for the two dosing regimens. There were no differences in the incidence of new vertebral fractures or the worsening of existing fractures between the once-weekly (2.2%) and once-daily (2.7%) dosing regimens. No significant differences were observed between the two dosing regimens in the incidence or the type of adverse events. However, 10.1% of the patients in the once-daily group withdrew due to adverse events as compared to 5.2% in the once-weekly group. Moreover, drug-related adverse events, including upper gastrointestinal disorders and abnormal changes in laboratory parameters, tended to be less in the once-weekly dosing regimen than in the once-daily dosing regimen. In conclusion, once-weekly oral dosing with 17.5 mg risedronate was well tolerated in Japanese osteoporotic patients, and showed equivalent efficacy to once-daily oral dosing with 2.5 mg risedronate. This once-weekly regimen is expected to provide a more convenient therapeutic option as an alternative to daily dosing and to enhance patient compliance in long-term therapy for Osteoporosis.
-
a comparison of incidences of vertebral fracture in japanese patients with Involutional Osteoporosis treated with risedronate and etidronate a randomized double masked trial
Journal of Bone and Mineral Metabolism, 2004Co-Authors: Kazuhiro Kushida, Hirotoshi Morii, Masao Fukunaga, Hideaki Kishimoto, Masataka Shiraki, Akira Itabashi, T Inoue, Kiyoshi Kaneda, Hajime Nawata, Kichizo YamamotoAbstract:To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of Involutional Osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200 mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (-0.28 cm) than in the etidronate group (-0.70 cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5 mg) was shown to provide an effective therapy for Involutional Osteoporosis in Japanese patients with good tolerability.
Masao Fukunaga - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of monthly oral minodronate in patients with Involutional Osteoporosis
Osteoporosis International, 2012Co-Authors: Ryo Okazaki, Masao Fukunaga, Masataka Shiraki, Hiroshi Hagino, Toshitaka Nakamura, Teruki Sone, Masako Ito, Hideki Mizunuma, Yoshiki Nishizawa, Yasuo OhashiAbstract:Summary Monthly minodronate at 30 or 50 mg had similar efficacy as 1 mg daily in terms of change in bone mineral density (BMD) and bone turnover markers with similar safety profiles. This new regimen provides patients with a new option for taking minodronate.
-
efficacy and tolerability of once weekly administration of 17 5 mg risedronate in japanese patients with Involutional Osteoporosis a comparison with 2 5 mg once daily dosage regimen
Journal of Bone and Mineral Metabolism, 2006Co-Authors: Hideaki Kishimoto, Kazuhiro Kushida, Masao Fukunaga, Masataka Shiraki, Akira Itabashi, Hajime Nawata, Toshitaka Nakamura, Hiroaki Ohta, Kunio Takaoka, Yasuo OhashiAbstract:In this multicenter, randomized, double-blind controlled trial, the efficacy and safety of once-weekly dosing with 17.5 mg risedronate was compared with once-daily dosing with 2.5 mg risedronate in Japanese patients with Involutional Osteoporosis. A total of 496 patients were randomized to receive either once-weekly (n = 249) or once-daily (n = 247) treatment. All patients were supplemented with 200 mg/day calcium. Following 48 weeks of treatment, the mean (±SD) percent changes, from baseline, in the bone mineral density of the lumbar spine (L2-L4 BMD) in the once-weekly and once-daily treatment groups were 5.36 ± 4.27% and 5.87 ± 4.47%, respectively. The difference between the groups was −0.5% (95% confidence interval: −1.35% to 0.35%), demonstrating that the effect on BMD of once-weekly treatment was not inferior to that of once-daily treatment. The time-course reductions in biochemical markers of bone resorption (urinary N- and C-telopeptide of type I collagen) and bone formation (bone-specific alkaline phosphatase) were similar for the two dosing regimens. There were no differences in the incidence of new vertebral fractures or the worsening of existing fractures between the once-weekly (2.2%) and once-daily (2.7%) dosing regimens. No significant differences were observed between the two dosing regimens in the incidence or the type of adverse events. However, 10.1% of the patients in the once-daily group withdrew due to adverse events as compared to 5.2% in the once-weekly group. Moreover, drug-related adverse events, including upper gastrointestinal disorders and abnormal changes in laboratory parameters, tended to be less in the once-weekly dosing regimen than in the once-daily dosing regimen. In conclusion, once-weekly oral dosing with 17.5 mg risedronate was well tolerated in Japanese osteoporotic patients, and showed equivalent efficacy to once-daily oral dosing with 2.5 mg risedronate. This once-weekly regimen is expected to provide a more convenient therapeutic option as an alternative to daily dosing and to enhance patient compliance in long-term therapy for Osteoporosis.
-
a comparison of incidences of vertebral fracture in japanese patients with Involutional Osteoporosis treated with risedronate and etidronate a randomized double masked trial
Journal of Bone and Mineral Metabolism, 2004Co-Authors: Kazuhiro Kushida, Hirotoshi Morii, Masao Fukunaga, Hideaki Kishimoto, Masataka Shiraki, Akira Itabashi, T Inoue, Kiyoshi Kaneda, Hajime Nawata, Kichizo YamamotoAbstract:To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of Involutional Osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200 mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (-0.28 cm) than in the etidronate group (-0.70 cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5 mg) was shown to provide an effective therapy for Involutional Osteoporosis in Japanese patients with good tolerability.
Kazuhiro Kushida - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and tolerability of once weekly administration of 17 5 mg risedronate in japanese patients with Involutional Osteoporosis a comparison with 2 5 mg once daily dosage regimen
Journal of Bone and Mineral Metabolism, 2006Co-Authors: Hideaki Kishimoto, Kazuhiro Kushida, Masao Fukunaga, Masataka Shiraki, Akira Itabashi, Hajime Nawata, Toshitaka Nakamura, Hiroaki Ohta, Kunio Takaoka, Yasuo OhashiAbstract:In this multicenter, randomized, double-blind controlled trial, the efficacy and safety of once-weekly dosing with 17.5 mg risedronate was compared with once-daily dosing with 2.5 mg risedronate in Japanese patients with Involutional Osteoporosis. A total of 496 patients were randomized to receive either once-weekly (n = 249) or once-daily (n = 247) treatment. All patients were supplemented with 200 mg/day calcium. Following 48 weeks of treatment, the mean (±SD) percent changes, from baseline, in the bone mineral density of the lumbar spine (L2-L4 BMD) in the once-weekly and once-daily treatment groups were 5.36 ± 4.27% and 5.87 ± 4.47%, respectively. The difference between the groups was −0.5% (95% confidence interval: −1.35% to 0.35%), demonstrating that the effect on BMD of once-weekly treatment was not inferior to that of once-daily treatment. The time-course reductions in biochemical markers of bone resorption (urinary N- and C-telopeptide of type I collagen) and bone formation (bone-specific alkaline phosphatase) were similar for the two dosing regimens. There were no differences in the incidence of new vertebral fractures or the worsening of existing fractures between the once-weekly (2.2%) and once-daily (2.7%) dosing regimens. No significant differences were observed between the two dosing regimens in the incidence or the type of adverse events. However, 10.1% of the patients in the once-daily group withdrew due to adverse events as compared to 5.2% in the once-weekly group. Moreover, drug-related adverse events, including upper gastrointestinal disorders and abnormal changes in laboratory parameters, tended to be less in the once-weekly dosing regimen than in the once-daily dosing regimen. In conclusion, once-weekly oral dosing with 17.5 mg risedronate was well tolerated in Japanese osteoporotic patients, and showed equivalent efficacy to once-daily oral dosing with 2.5 mg risedronate. This once-weekly regimen is expected to provide a more convenient therapeutic option as an alternative to daily dosing and to enhance patient compliance in long-term therapy for Osteoporosis.
-
a comparison of incidences of vertebral fracture in japanese patients with Involutional Osteoporosis treated with risedronate and etidronate a randomized double masked trial
Journal of Bone and Mineral Metabolism, 2004Co-Authors: Kazuhiro Kushida, Hirotoshi Morii, Masao Fukunaga, Hideaki Kishimoto, Masataka Shiraki, Akira Itabashi, T Inoue, Kiyoshi Kaneda, Hajime Nawata, Kichizo YamamotoAbstract:To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of Involutional Osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200 mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (-0.28 cm) than in the etidronate group (-0.70 cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5 mg) was shown to provide an effective therapy for Involutional Osteoporosis in Japanese patients with good tolerability.
-
circadian rhythm of the urinary crosslinks pyridinoline and deoxypyridinoline in normal human and Involutional Osteoporosis
Journal of Bone and Mineral Metabolism, 1996Co-Authors: H Aoshima, Kazuhiro Kushida, Masaaki Takahashi, Tsuyoshi Ohishi, K Kawana, Tetsuo InoueAbstract:Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are collagen crosslinks found in bone and cartilage and are sensitive bone resorption markers. In this study, values of urinary Pyr and Dpyr during 24-h periods in 6 normal men, 10 normal women, and 10 osteoporotic patients were measured. In these three groups, urinary Pyr and Dpyr showed significant circadian variations only in normal men. Neither urinary Pyr nor Dpyr showed significant circadian variations in normal women or osteoporotic subjects, although they had the same trend as the diurnal changes of urinary crosslinks in normal men. Comparing the values of urinary crosslinks in the daytime (11:00–20:00 h) and at night (20:00–11:00 h), the latter were significantly higher than the former in both normal and osteoporotic subjects. Furthermore, the nighttime and daytime difference of urinary Pyr in osteoporotic subjects was significantly larger than those in normal subjects. Urinary Pyr and Dpyr were 22.6% and 10.7% higher, respectively, at night compared to during the day in normal women, while in osteoporotic patients, the values were 51.2% and 25.5% higher at night than during the day, respectively. In conclusion, the acceleration of bone resorption at night may be one of the etiologies of Involutional Osteoporosis.
-
utility of diagnostic criteria for Involutional Osteoporosis established by the japanese ministry of health and welfare
Journal of Bone and Mineral Metabolism, 1993Co-Authors: Kaoru Yamazaki, Kazuhiro Kushida, Akihiro Ohmura, Tetsuo InoueAbstract:We conducted a study to determine whether the draft criterion for the diagnosis of Involutional Osteoporosis proposed by the Silver Science Research Group of the Ministry of Health and Welfare have achieved a widespread consensus.
E Schacht - One of the best experts on this subject based on the ideXlab platform.
-
rationale for treatment of Involutional Osteoporosis in women and for prevention and treatment of corticosteroid induced Osteoporosis with alfacalcidol
Calcified Tissue International, 1999Co-Authors: E SchachtAbstract:Increased cytokine release and increased activity of osteoclasts (reduced osteoclast apoptosis) due to a fall in estrogen is of causal significance in postmenopausal bone loss as well as malfunction of the vitamin D activation and concomitant calcium (Ca) malabsorption. Alfacalcidol prevents rapid postmenopausal bone loss by elimination of Ca malabsorption and by blocking resorbing cytokines.
-
rationale for treatment of Involutional Osteoporosis in women and for prevention and treatment of corticosteroid induced Osteoporosis with alfacalcidol
Calcified Tissue International, 1999Co-Authors: E SchachtAbstract:Increased cytokine release and increased activity of osteoclasts (reduced osteoclast apoptosis) due to a fall in estrogen is of causal significance in postmenopausal bone loss as well as malfunction of the vitamin D activation and concomitant calcium (Ca) malabsorption. Alfacalcidol prevents rapid postmenopausal bone loss by elimination of Ca malabsorption and by blocking resorbing cytokines. Established Osteoporosis in older patients of both sexes is characterized by decoupled bone remodeling induced by sex hormone deficits and by a so-called somatopause (insulin-like growth factor [IGF]-deficit), but also by lack of vitamin D and, very importantly, by reduced synthesis of D-hormone (Calcitriol) in kidneys and bone as well as by a lack of receptors or receptor affinity for D-hormone in the target organs. As a consequence of these facts, a rise in parathormone (PTH) frequently occurs. The lack of D-hormone and IGF-1 evidently causes a reduction in muscle strength as well and reinforces the risk of falling and, thus, the risk of a fracture. Alfacalcidol, a prodrug of D-hormone, is a specific antiosteoporotic therapy. In alfacalcidol therapy, D-hormone is provided to the body in circumvention of its own regulation, by means of which much higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. Chances have been significantly improved of reducing and frequently preventing the real Osteoporosis complication for older male and female patients, i. e., bone fractures, by alfacalcidol. A clear distinction should be made between supplementation with low-dosed plain vitamin D and calcium as base supply in elderly housebound subjects or as adjuvant to antiosteoporotic drugs and the specific antiosteoporotic therapy with alfacalcidol in patients with Osteoporosis. The expanded understanding of the pathogenesis of corticosteroid-induced Osteoporosis with its disturbed Ca homeostasis and the pharmacological effects of alfacalcidol, counteracting such iatrogenic bone loss, explain the particularly good clinical efficacy in this most frequent form of secondary Osteoporosis. Normalizing de-coupled bone remodeling due to cytokine modulation and the potential influence on deteriorated bone quality in patients with rheumatoid arthritis and Crohn's disease predestine this form of therapy for prevention and treatment of Osteoporosis as a result of chronic inflammatory diseases as well as of transplantation Osteoporosis cases in particular.
