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IntroductionEldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients.Materials and methodsA randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 μg eldecalcitol compared with 1.0 μg alfacalcidol in GIO patients.ResultsLumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24 months (between group difference 1.29%, p < 0.01, and 1.10%, p < 0.05, respectively). Total hip and femoral neck BMD were maintained until 24 months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%, p < 0.05 and 1.22%, p < 0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups.ConclusionsEldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO.Clinical trial registration numberUMIN000011700.

Alfacalcidol and paricalcitol are vitamin D analogs used for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease, but have known dose-dependent side effects that cause hypercalcemia and hyperphosphatemia. In this investigator-initiated multicenter randomized clinical trial, we originally intended two crossover study periods with a washout interval in 86 chronic hemodialysis patients. These patients received increasing intravenous doses of either alfacalcidol or paricalcitol for 16 weeks, until parathyroid hormone was adequately suppressed or calcium or phosphate levels reached an upper threshold. Unfortunately, due to a period effect, only the initial 16-week intervention period for 80 patients was statistically analyzed. The proportion of patients achieving a 30% decrease in parathyroid hormone levels over the last four weeks of study was statistically indistinguishable between the two groups. Paricalcitol was more efficient at correcting low than high baseline parathyroid hormone levels, whereas alfacalcidol was equally effective at all levels. There were no differences in the incidence of hypercalcemia and hyperphosphatemia. Thus, alfacalcidol and paricalcitol were equally effective in the suppression of secondary hyperparathyroidism in hemodialysis patients while calcium and phosphorus were kept in the desired range.

IntroductionThis study compared the clinical usefulness of minodronate (50 mg/4 weeks) plus alfacalcidol (1 μg/day) (Group M) with that of alfacalcidol alone (1 μg/day) (Group A) for treating glucocorticoid-induced osteoporosis.Materials and methodsThe primary endpoints were the changes from baseline in lumbar spine (LS) bone mineral density (BMD) and the cumulative incidence of vertebral fracture at 24 months; secondary endpoints included the changes from baseline in total hip (TH) BMD and bone turnover markers.ResultsOf 164 patients enrolled, 152 (Group M, n = 75; Group A, n = 77) were included in the analysis of efficacy. At each time point and at 24 months, LS BMD and TH BMD were significantly higher in Group M than in Group A. The 152 patients were divided into two subgroups that were previously treated with glucocorticoids for ≤ 3 months or > 3 months. In both subgroups, the changes from baseline in LS BMD and TH BMD from baseline at 24 months had increased more in Group M than in Group A. There were no differences found in the incidence of vertebral fracture between the groups, because the number of enrolled patients was lesser than that initially expected. In Group M, both bone formation and resorption markers significantly decreased from baseline at 3 months and maintained at 6, 12, and 24 months.ConclusionsMinodronate plus alfacalcidol was more effective than alfacalcidol alone in increasing BMD and was effective in increasing BMD for both prevention and treatment. Therefore, minodronate can be a good candidate drug for the treatment of glucocorticoid-induced osteoporosis.

A combined therapy with the strongly antiresorptive Alendronate and the pleiotropically acting D-hormone analogue Alfacalcidol may have additive effects on bone quality, falls and fracture risk in established osteoporosis. The aim of this study (Alfacalcidol Alendronate Combined-AAC) was to compare the efficacy and safety of a combined parallel therapy with Alendronate and Alfacalcidol to the treatment with either Alendronate in combination with plain vitamin D or Alfacalcidol alone in patients with established postmenopausal or male osteoporosis. Ninety patients were included as matched triplets to receive randomly either 1 microg Alfacalcidol daily + 500 mg calcium (group A, n = 30) or 70 mg Alendronate weekly + 1,000 mg calcium + 1,000 IU vitamin D daily (group B, n = 30) or 1 microg Alfacalcidol daily + 70 mg Alendronate weekly + 500 mg calcium daily (group C, n = 30). Patients were recruited in one centre and were followed up for 24 months. Analysis was intention-to-treat and the primary outcome was lumbar spine and total hip bone mineral density (measured observer blind). BMD was measured at the lumbar spine and at the proximal femur with dual energy X-ray absorptiometry (LUNAR Prodigy, GE, USA) at the beginning and after 12 and 24 months. During the 2-year-study we observed descriptively significant increases at the lumbar spine of 3.0% in group A compared to baseline, of 5.4% in group B and of 9.6% in group C, respectively. The superiority of the Alendronate + Alfacalcidol treatment group over Alfacalcidol alone and over Alendronate + vitamin D was of more than large rele-vance (both tests: MW > 0.71; CI-LB > 0.64; P < 0.001). We also observed median increases of the BMD at the total hip of 1.5% in group A, of 2.4% in group B and of 3.8% in group C, respectively. The superiority of group C over group A and over group B again was relevant and statistically significant in a descriptive sense. After 2 years there was a tendency towards higher rates of vertebral and non-vertebral fractures in group A and B as compared to C. Taking both fracture types together we observed 9, 10 and 2 \"osteoporotic fractures\" in groups A, B and C, respectively. The comparison of group C with pooled groups A and B and with each single group gave a relevantly lower fracture rate for the combination of Alendronate and Alfacalcidol. Furthermore a lower rate of falls was observed for the combination Alendronate plus Alfacalcidol versus Alendronate + vitamin D, but not versus Alfacalcidol alone. We found 80% of the patients in the Alendronate + Alfacalcidol group free from back pain at month 24, compared to 30% in the Alendronate + vitamin D and 43% in the Alfacalcidol monotherapy group. The superiority is relevant (both tests: MW > 0.64; CI-LB > 0.56; P < 0.003). Pain decrease also occurred more rapidly in the Alendronate + Alfacalcidol group than in the other groups. In general side effects in all groups were mild, and only four cases of moderate hypercalcuria in group A and one in group C were reported, but no case of hypercalcemia was documented. In conclusion, the combination therapy with Alendronate and Alfacalcidol exhibited superiority in terms of BMD, overall fractures, rate of falls and back pain over either Alendronate in combination with plain vitamin D or Alfacalcidol alone. The overall safety profiles of the three treatment regimens were found to be not different in this study.

We previously observed that a creatinine clearance (CrCl) of <65 ml/min is a significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels. To test our hypothesis, we investigated in a post hoc analysis of a double-blind randomized study whether treatment with alfacalcidol, a synthetic prodrug of the D-hormone, can reduce the high incidence of fallers and the high risk of falls associated with low CrCl. Of 378 Swiss community-dwelling women (n=191) and men (n=187), aged 70 years and older, 191 received randomly 1 microg capsules of alfacalcidol (AlphaD3: Teva), and 187 received one capsule of placebo daily. With the help of questionnaires we regularly assessed the incidence and frequency of falls. The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65 ml/min. The presented results are from ITT analyses. In participants with a CrCl of <65 ml/min, the 36 weeks of treatment with alfacalcidol was, compared with placebo, associated with a significant reduction in the number of fallers (14/72 versus 25/70; OR 0.26, 95% CI 0.08-0.80, P=0.019), and a significant reduction of the number of falls (16/72 versus 28/70; OR 0.29, 95% CI 0.09-0.88, P=0.028). No such association was observed in participants with a CrCl of >or=65 ml/min (for fallers 26/120 versus 21/116; OR 0.92 95% CI 0.34-2.52, P=0.875; for falls 32/120 versus 23/116; OR 0.93 95% CI 0.34-2.54, P=0.885). In the placebo group frequency of falls was dependent on CrCl (P=0.006), whereas in the alfacalcidol treatment group frequency of falls was independent of CrCl (P=0.494). No cases of clinically relevant hypercalcemia were observed. In a community-dwelling population of elderly men and women with a CrCl of <65 ml/min, treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of falls.

Due to pleiotropic-synergistic actions on bone, muscle, gut, brain and different other non-skeletal tissues, alfacalcidol is an interesting drug for treating osteoporosis. In studies on glucocorticoid-induced osteoporosis, men have always been treated with calcitriol or this active D-hormone prodrug, but there is no study of male patients only in the literature. The AIM-Trial (Alfacalcidol In Men) is an extension of the control group ( n  = 158) of our former risedronate study in male osteoporosis (Ringe et al. in Rheumatol Int 29:311–315, 2009 ). In that study, we treated daily those controls with prevalent vertebral fractures with 1 μg alfacalcidol + 500 mg calcium (group A) and those without prevalent vertebral fractures with 1,000 IU plain vitamin D (Vit. D) + 1,000 mg calcium (group B). Subsequently, we added an additional 56 pairs of patients to these two groups: 28 with and 28 without prevalent vertebral fractures, reaching a total of 214 cases. That means with this design, we are comparing two groups with a different risk at onset. Due to the prevalent vertebral fractures and lower average bone mineral density (BMD) values, there was a higher risk of incident fractures in group A. After 2 years, we found significantly higher increases in lumbar spine BMD (+3.2 vs. +0.8 %) and total hip BMD (+1.9 vs. −0.9 %) in group A and B, respectively. Eighteen incident falls were recorded in the alfacalcidol group and 38 in the group treated with Vit. D ( p  = 0.041). There were significantly lower rates of patients with new vertebral and non-vertebral fractures in group A than in group B. Back pain was significantly reduced only with alfacalcidol. Concerning the incidence of new non-vertebral fractures, we found that there was a relation to renal function in the two groups. The advantage for alfacalcidol was mainly due to a higher non-vertebral fracture-reducing potency in patients with a creatinine clearance (CrCl) below 60 ml/min ( p  = 0.0019). There were no serious adverse events (SAE), and the numbers of mild-to-moderate adverse events (AE) were not different between groups. Despite the higher initial fracture risk in the alfacalcidol group, 2-year treatment with this active D-hormone prodrug showed a higher therapeutic efficacy in terms of BMD, falls and fractures. One important advantage of alfacalcidol may be that it is effective even in patients with mild-to-moderate renal insufficiency.

Patients who are diagnosed with osteoporosis and beginning treatment often discontinue their osteoporosis medication relatively early after the start of treatment because of their poor recognition of fracture risk and the asymptomatic nature of osteoporosis. In this study we aimed to assess adherence to treatment with 1 μg alfacalcidol (D), 60 mg raloxifene (R) or a combination of both (D + R) for 1 year in postmenopausal Japanese women with osteoporosis or osteopenia. We defined persistence of D and R as continuing to take tablets for more than 7 of any 14 days immediately before the 1-year visit. A total of 137 subjects aged 49-81 years [64.9 ± 7.0 years, 16.0 ± 12.7 years since menopause (YSM)] were randomly assigned to each treatment group. The proportions persisting with each treatment group at 1 year were 61.4, 65.3, 55.1% for D, R and D + R groups, respectively whereas the compliance to each therapy as judged by the medical possession ratio (MPR) at 1 year were 77.5, 93.8, 78.4%, respectively. There were no significant differences in persistence, compliance and the number of subjects who discontinued treatment due to adverse events among each group. We found significant inverse correlations in percent changes at 1 year between compliance and serum BAP in R and D + R groups or urinary (u-) CTX in the R group. The changes in the level of serum BAP and u-CTX were significantly higher in high-compliance patients (MPR > 80%) treated with raloxifene alone or concomitantly with alfacalcidol compared to those in low-compliance patients.

A randomized, double-blind, prospective, 24-week clinical trial was performed to evaluate the effects of a combinative agent, Maxmarvil, of calcitriol (0.5 mug) and alendronate (5 mg) on bone metabolism in postmenopausal women. A total of 217 postmenopausal women with osteoporosis were enrolled; 199 patients were randomly assigned to one of two treatment groups (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D-deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they received any drugs affecting bone metabolism before enrollment. Bone mineral densities (BMD) of L1-L4 and the femur were measured by dual-energy X-ray absorptiometry (DXA) at the initial assessment and after 6 months of treatment. Serum biochemical assays, including serum calcium, 24-h urinary calcium excretion, and bone turnover markers (both bone-specific alkaline phosphatase [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after 3 and 6 months of treatment. In the Maxmarvil group, the BMD of the lumbar spine increased up to 2.42+/-0.5% from the baseline after 6 months (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was 0.28+/-0.5% after 6 months. There was no significant difference in femoral BMD between the two groups. The levels of bsALP and NTx were significantly lower in the Maxmarvil group than in the alfacalcidol group (-22.04+/-3.9% vs. -11.42+/-2.8% [p<0.05] and -25.46+/-5.2% vs. 1.24+/-6.2% [p<0.001], respectively). Interestingly, there was a significantly smaller amount of 24-h urinary calcium in the Maxmarvil group (p<0.05). Our study demonstrates that a combination of calcitriol and alendronate is quite effective in preventing bone loss, with the advantage of lesser hypercalciuric effect of calcitriol in the postmenopausal osteoporotic women.

ObjectivesThis cross-sectional study aims to evaluate the association between calcium and vitamin D supplementation for osteoporosis treatment and the development of kidney stones while investigating the impact of urinary calcium excretion on kidney stone risk among patients receiving this supplementation treatment.DesignThe study involved collecting data from 204 Chinese Han patients aged 50–89 with osteoporosis in the southwest region of China. These patients had been on daily doses of 600 mg of calcium carbonate and 0.5 µg alfacalcidol for at least 1 year. The study employed univariate analysis and multivariable logistic regression to identify risk factors for kidney stones, with independent t-tests used to compare differences between groups.SettingData were collected from patients in the southwest region of China, covering the period from July 2019 to December 2023.ParticipantsThe study included 204 patients with osteoporosis, all of whom had been receiving the specified calcium and vitamin D supplements for the duration of the study.ResultsThe study found that a history of recurrent kidney stones was an independent risk factor for the development of kidney stones. Patients with kidney stones who had a history of recurrent stones exhibited significantly higher levels of 24-hour urinary calcium excretion (1.00±0.62 vs 0.57±0.54, p=0.026) compared with those without such a history.ConclusionsThe results suggest that a history of recurrent kidney stones independently increases the risk of kidney stones in patients undergoing calcium and vitamin D supplementation for osteoporosis, likely due to increased urinary calcium excretion.

Abstract Context Patients with hypoparathyroidism are treated with vitamin D and calcium. PTH is an emerging option because of its physiological action. It is important to assess the efficacy and shortcomings of conventional therapy. Objective We assessed the efficacy and safety of alfacalcidol in a large cohort of patients with idiopathic hypoparathyroidism (IH) and identified a subset who could be treated without oral calcium. Design and Setting Observational study at tertiary care center. Subjects and Methods We assessed 92 patients with IH who were receiving alfacalcidol and oral calcium to maintain an optimal serum total calcium level of 8.0 to 8.5 mg/dL during routine follow-up. Patients with suboptimal control were provided free medicines and followed up frequently. Oral calcium and alfacalcidol doses were titrated sequentially to determine the minimum doses for optimal calcium control. Serum phosphate level, 1,25-dihydroxyvitamin D, fractional excretion of phosphorus (FEPh), and hypercalciuria (urine calcium-to-creatinine ratio, >0.2) were assessed at each step of titration. Results Only 38% of patients had optimal calcium control during routine follow-up. With good compliance, all achieved optimal serum calcium and 1,25-dihydroxyvitamin D levels and 43% of patients could stop taking oral calcium. Hyperphosphatemia, hypercalciuria, and low FEPh persisted at all stages of therapy. Serum phosphorus levels normalized when the serum calcium level increased to 9.9 mg/dL, but this level of serum total calcium was associated with hypercalciuria in 90% of patients. Conclusion Alfacalcidol is effective in achieving calcemic control in IH. Calcemic control without oral calcium was achieved in 43% of patients receiving alfacalcidol. However, optimal calcium control was associated with hyperphosphatemia and hypercalciuria in most patients. Alfacalcidol is effective in calcemic control of IH; 43% achieved it without oral calcium. However, optimal calcemic control was associated with hyperphosphatemia and hypercalciuria in most patients.