The effect of 1-hydroxy-vitamin D treatment in hospitalized patients with COVID-19: A retrospective study.

BACKGROUND & AIMS: The efficacy of vitamin D supplementation in coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to evaluate the effect of 1-hydroxy-vitamin D on the prevention of severe disease and mortality in patients hospitalized for COVID-19. METHODS: This retrospective study included 312 patients with COVID-19 who were admitted to our hospital between April 2021 and October 2021 (primarily the Delta variant) and between July 2022 and September 2022 (primarily Omicron variant). Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at the time of admission and 1-hydroxy-vitamin D was prescribed by the treating physicians. The patients were divided into two groups: those administered 1-hydroxy-vitamin D (Vit D group) and those who were not (control group). The composite primary endpoint was the need for additional respiratory support, including high-flow oxygen therapy or invasive mechanical ventilation, and in-hospital mortality rate. RESULTS: Of 312 patients, 122 (39%) received 1-hydroxy-vitamin D treatment. Although the median age was not significantly higher in the Vit D group than in the control group (66 vs. 58 years old, P = 0.06) and there was no significant difference in the proportion of vitamin D deficiency (defined as serum 25(OH)D level less than 20 ng/mL, 77% vs. 65%, P = 0.07), patients in the control group had a more severe baseline profile compared to the Vit D group according to the Japanese disease severity definition for COVID-19 (P = 0.01). The proportion of those requiring more respiratory support and in-hospital mortality was significantly lower in the Vit D group than in the control group (6% vs. 14%, P = 0.01 log-rank test). After propensity score matching, a statistically significant difference in the primary endpoint was observed (P = 0.03 log-rank test). CONCLUSIONS: 1-hydroxy-vitamin treatment may improve outcomes in hospitalized patients with COVID-19, reducing composite outcomes including the need for additional respiratory support and in-hospital mortality.

Clinical efficacy and safety of use of alfacalcidol and calcitriol in daily endocrinological practice.

This paper aims to discuss and compare 2 vitamin D derivatives available on the Polish market, alfacalcidol and calcitriol, in the context of their effectiveness and safety in endocrine patients. Both above-mentioned substances find a number of applications, including in hypoparathyroidism, which is one of the most common indications for their use. We would also like to draw the reader's attention to the fact that there are quite a lot of reports in the literature on the positive effect of alfacalcidol and calcitriol on maintaining bone mass and the risk of fractures, which may bring additional potential benefits to our patients.

Dialysate calcium, alfacalcidol, and clinical outcomes: A post-hoc analysis of the J-DAVID trial.

The selection of dialysate calcium concentration (D-Ca) is still controversial among chronic hemodialysis (HD) regimens. We examined the trajectories of CKD MBD parameters among the J-DAVID trial participants to see the effect of D-Ca and alfacalcidol. The trial was an open-label randomized clinical trial including 976 HD patients with intact PTH of 180 pg/mL or lower which compared the users of vitamin D receptor activator (oral alfacalcidol) and non-users over a median of 4 years. The main D-Ca used at baseline were 3.0 mEq/L in 70% and 2.5 mEq/L in 25%, respectively. The primary endpoint was the composite of fatal and non-fatal cardiovascular events and the secondary endpoint was all-cause mortality. Multivariable Cox proportional hazard regression analyses in which D-Ca was included as a possible effect modifier and serum laboratory data as time-varying covariates showed no significant effect modification for composite cardiovascular events or all-cause mortality. This post hoc analysis showed that the effects of alfacalcidol on cardiovascular outcomes were not significantly modified by D-Ca.

Effects of alfacalcidol on cardiovascular outcomes according to alkaline phosphatase levels in the J-DAVID trial.

In the Japan Dialysis Active Vitamin D (J-DAVID) trial, oral alfacalcidol numerically, but not significantly, increased the risk of cardiovascular events among patients undergoing hemodialysis. Because the cardiovascular effect of alfacalcidol could be modulated by bone turnover status, this post-hoc analysis of the J-DAVID examined how alkaline phosphatase (ALP), a more precise marker of bone turnover than parathyroid hormone (PTH), modifies the impact of alfacalcidol. The J-DAVID was a 48-month, open-label, randomized controlled trial comparing oral alfacalcidol with no vitamin D receptor activators use in terms of cardiovascular events among 976 hemodialysis patients without secondary hyperparathyroidism. This post-hoc analysis included 959 patients with available data on baseline ALP. The median [25-75th percentile] baseline ALP level was 234 [183-296] U/L. In a Cox proportional hazards model, ALP did not significantly modify the effect of alfacalcidol on the rate of cardiovascular events or all-cause death (P for effect modification = 0.54 and 0.74, respectively). The effect of alfacalcidol on time-series changes in calcium, phosphate, and intact PTH were similar across ALP subgroups. In conclusion, oral alfacalcidol did not significantly affect cardiovascular outcomes irrespective of bone turnover status.

VITAMIN D AND OPHTHALMOPATHIAS. A REVIEW.

The importance of vitamin D3 (hydroxycholecalciferol) as one of the liposoluble vitamins is known in the prevention and treatment of metabolic bone diseases (rickets, osteomalacia, osteoporosis). In recent years, however, information has increased on the importance of vitamin D3 in numerous organ systems and in the pathogenesis of various diseases, e. g. ophthalmopathies. The immunological functions of vitamin D3 are the subject of studies dealing with autoimmune optic nerve disorders and their results appear to have a positive effect on demyelinating diseases. It also plays an important role in maintaining the thickness of the retinal nerve fiber layer, but its additional administration has not been successful. Optical neuritis may be the first sign of multiple sclerosis. It appears that sufficient serum vitamin D3 levels may protect patients from deterioration in the form of a further attack of demyelination. The course of diabetic retinopathy is probably also influenced by vitamin D3, inter alia, by correlating the fact that its receptor and the enzymes of its metabolism are expressed on the retina. Low serum levels of vitamin D3 may even trigger age-related macular degeneration. Conversely, higher dietary intake of vitamin D3 may positively affect neovascularization. The optimal level of hydroxycholecalciferol is between 60 and 200 nmol /l, the severe deficit represents a decrease below 25 nmol/l. The body can normally produce up to 10,000 IU of this vitamin after exposure to sunlight. However, the demonstration of its protective character in connection with the mentioned diseases of the retina and optic nerve will require a sufficient number of studies to confirm the facts found so far about this rediscovered vitamin.

1α, 25-Dihydroxyvitamin D3 protects gastric mucosa epithelial cells against Helicobacter pylori-infected apoptosis through a vitamin D receptor-dependent c-Raf/MEK/ERK pathway.

CONTEXT: Due to the resistance of Helicobacter pylori to antibiotics, it is difficult to eradicate this pathogenic bacterium from the host. The role of 1α, 25-dihydroxyvitamin D3 (1,25-D3) in H. pylori-infected gastric mucosa epithelial cells remains unknown. OBJECTIVE: This study investigates the protective property of 1,25-D3 against H. pylori-infected apoptosis in gastric mucosa epithelial cells and its potential molecular mechanisms. MATERIALS AND METHODS: GES-1 cells were infected with H. pylori SS1 strain (MOI: 100) and treated with 1,25-D3 at 100, 200, and 300 nM for 24 h. Mice were orally gavaged with 108 CFUs of H. pylori and 25 µg/kg 1,25-D3 every other day for 1 month. CCK-8, LDH assay, TUNEL assay and western blot were used to determine the effect of 1,25-D3 on H. pylori-induced apoptosis. RESULTS: H. pylori infection decreased cell viability to 59.2%, while 100-300 nM 1,25-D3 increased cell viability to 62.2%, 78.4% and 87.1%, respectively. Compared with positive control (4.53-fold), 1,25-D3 reduced caspase-3 activity to 4.49-, 2.88- and 1.49-fold, reduced caspase-6 activity to 2.36-, 1.88- and 1.50-fold, reduced caspase-9 activity to 4.55-, 2.91- and 2.01-fold. 1,25-D3 alters Bcl-2 family, caspase protein expression and c-Raf/MEK/ERK phosphorylation levels in vivo and in vitro. Suppression of 1,25-D3 in apoptosis was reliant on binding to vitamin D receptor. The pharmacological inhibition of c-Raf/MEK/ERK phosphorylation blocked the anti-apoptotic effect of 1,25-D3. DISCUSSION AND CONCLUSION: 1,25-D3 protected gastric mucosa epithelial cells against H. pylori-infected apoptosis through a VDR-dependent c-Raf/MEK/ERK pathway.

Clinical effect of alfacalcidol in children with Henoch-Schönlein purpura: a prospective randomized controlled trial. / é˜¿æ³•éª¨åŒ–é†‡æ²»ç–—å„¿ç«¥è¿‡æ•æ€§ç´«ç™œçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the effects of alfacalcidol on serum 25-(OH)D3 level, cellular immune function, and inflammatory factors in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 200 children with HSP were prospectively enrolled from June 2018 to June 2020. According to the random number table method, they were divided into an observation group and a control group (n=100 each). The control group was treated with vitamin C, rutin tablets, dipyridamole, cimetidine, calcium supplements, and glucocorticoids. In addition to the treatment for the control group, the observation group received alfacalcidol capsules (0.25 µg/d) orally before bed for 4 weeks. The two groups were compared in terms of the level of 25-(OH)D3, the percentages of T lymphocyte subsets (CD3+, CD4+, and CD8+) and NK cells, and the levels of inflammatory factors, interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-21 (IL-21), and tumor necrosis factor-α (TNF-α), before treatment and after 4 weeks of treatment. The children were followed up for 6 months to determine the recurrence rate and the incidence of renal damage. RESULTS: After treatment, the observation group showed a significantly higher serum 25-(OH)D3 level, significantly higher percentages of CD3+T cells, CD4+T cells, and NK cells, and significantly lower levels of IL-6, IL-17, IL-21, and TNF-α compared with the control group (P<0.05). After 6 months of follow-up, the recurrence rate and the incidence of renal damage in the observation group were significantly lower than those in the control group (P<0.05). CONCLUSIONS: Alfacalcidol can increase the serum 25-(OH)D3 level, improve cellular immune function, decrease inflammatory factor levels, and reduce recurrence and renal damage in children with HSP.

Bisphosphonate use in children with cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is a heterogeneous group of non-progressive disorders of posture or movement, caused by a lesion of the developing brain. Osteoporosis is common in children with cerebral palsy, particularly in children with reduced gross motor function, and leads to an increased risk of fractures. Gross motor function in children with CP can be categorised using a tool called the Gross Motor Function Classification System (GMFCS). Bisphosphonate increases bone mineral density (BMD) and reduces fracture rates. Bisphosphonate is used widely in the treatment of adult osteoporosis. However, the use of bisphosphonate in children with CP remains controversial, due to a paucity of evidence and a lack of recent trials examining the efficacy and safety of bisphosphonate use in this population. OBJECTIVES: To examine the efficacy and safety of bisphosphonate therapy in the treatment of low BMD or secondary osteoporosis (or both) in children with cerebral palsy (GMFCS Levels III to V) who are under 18 years of age. SEARCH METHODS: In September 2020, we searched CENTRAL, MEDLINE, Embase, six other databases, and two trial registers for relevant studies. We also searched the reference lists of relevant systematic reviews, trials, and case studies identified by the search, and contacted the authors of relevant studies in an attempt to identify unpublished literature. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs), and quasi-RCTs, comparing at least one bisphosphonate (given at any dose, orally or intravenously) with placebo or no drug, for the treatment of low BMD or osteoporosis in children up to 18 years old, with cerebral palsy (GMFCS Levels III to V). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We were unable to conduct any meta-analyses due to insufficient data, and therefore provide a narrative assessment of the results. MAIN RESULTS: We found two relevant RCTs (34 participants). Both studies included participants with non-ambulatory CP or CP and osteoporosis. Participants in both studies were similar in severity of CP, age distribution, and sex distribution. The two trials used different bisphosphonate medications and different intervention durations, but further comparison of the interventions was not possible due to a lack of published data from one trial. One trial received funding and support from research, academic, and hospital foundations, with pharmaceutical companies providing components of the calcium and vitamin supplement; the other trial did not report sources of funding. We judged one study at an overall high risk of bias; the other as overall unclear risk of bias. PRIMARY OUTCOME: Compared to placebo or no treatment, both studies provided very low certainty evidence of improved BMD at least four months post-intervention in children treated with bisphosphonate. Only one study (12 participants) provided sufficient detail to assess a measure of the effect, and reported an improvement at six months post-intervention in lumbar spine z-score (mean difference (MD) 18%, 95% confidence interval (CI) 6.57 to 29.43; very low certainty evidence). SECONDARY OUTCOMES: Very low certainty evidence from one study found that bisphosphonate reduced serum N-telopeptides (NTX) more than placebo; the other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced NTX, but did not compare groups. One study reported inconclusive results between groups for serum bone-specific alkaline phosphatase (BAP). The other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced BAP, but did not compare groups. Neither study reported data for the effect of bisphosphonate treatment on changes in volumetric BMD in the distal radius or tibia, changes in fracture frequency, bone pain, or quality of life. One study reported that two participants had febrile events noted during their first dosing schedule, but no further adverse events were reported in either relevant study. AUTHORS' CONCLUSIONS: Based on the available evidence, there is very low certainty evidence that bisphosphonate treatment may improve bone health in children with cerebral palsy. We could only include one study with 14 participants in the assessment of the effect size; therefore, the precision of the effect estimate is low. We could only evaluate one planned primary outcome, as there was insufficient detail reported in the relevant studies. Further research from RCTs on the effect and safety of bisphosphonate to improve bone health in children with cerebral palsy is required. These studies should clarify the optimal standard treatment regarding weight-bearing exercises, vitamin D and calcium supplementation, and should include fracture frequency as a primary outcome.

Could Vitamin D3 Deficiency Influence Malocclusion Development?

The abnormal growth of the craniofacial bone leads to skeletal and dental defects, which result in the presence of malocclusions. Not all causes of malocclusion have been explained. In the development of skeletal abnormalities, attention is paid to general deficiencies, including of vitamin D3 (VD3), which causes rickets. Its chronic deficiency may contribute to skeletal malocclusion. The aim of the study was to assess the impact of VD3 deficiency on the development of malocclusions. The examination consisted of a medical interview, oral examination, an alginate impression and radiological imaging, orthodontic assessment, and taking a venous blood sample for VD3 level testing. In about 42.1% of patients, the presence of a skeletal defect was found, and in 46.5% of patients, dentoalveolar malocclusion. The most common defect was transverse constriction of the maxilla with a narrow upper arch (30.7%). The concentration of vitamin 25 (OH) D in the study group was on average 23.6 ± 10.5 (ng/mL). VD3 deficiency was found in 86 subjects (75.4%). Our research showed that VD3 deficiency could be one of an important factor influencing maxillary development. Patients had a greater risk of a narrowed upper arch (OR = 4.94), crowding (OR = 4.94) and crossbite (OR = 6.16). Thus, there was a link between the deficiency of this hormone and the underdevelopment of the maxilla.

The relationship between serum hydroxyvitamin D levels and fall risks in young adults.

INTRODUCTION: Serum hydroxyvitamin D [25(OH)D] has a role in several aspects of physical performance. Our aim was to determine the possible association between serum 25(OH)D deficiency on the fall risk in young adults by using an objective computerized technique. MATERIALS AND METHODS: This cross-sectional study included 80 adults aged 18-40 years with 25(OH)D deficiency and 40 age-matched controls. The participants were devided into three groups according to serum 25(OH)D levels: Group 1; deficient, Group 2; insufficient and Group 3; sufficient (serum 25(OH)D level < 20, 20 to < 30 and 30-100 ng/mL, respectively). The age, gender, height and weight were recorded. To evaluate the fall risk, the Berg Balance test as a clinical assessment and a computerised posturography devise as an objective technique were used. Serum 25(OH)D levels were analyzed by ELISA. Pearson Chi-square, the Kruskal Wallis and Spearman correlation tests were used for statistical analysis. RESULTS: 42 male and 78 female participants were evaluated. In posturographic evaluation, although fall risk score was the highest in group 1 and the lowest in group 3, these differences could not reach statistical significance. However, statistically significant higher fall risk was found in participants with 25(OH)D deficiency (25(OH)D< 30) than in controls (25(OH)D> 30) (p = 0.036). Also a statistically significant correlation was determined between serum 25(OH)D levels and the posturography fall risk scores (p = 0.016, r = - 0, 219). CONCLUSION: By using an objective computerized technique, fall risk was found to be higher in young adults with 25(OH)D deficiency than in the controls. Vitamin D deficiency, even when clinically occult, seems to affect balance negatively.

Use of pre-operative calcium and vitamin D supplementation to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy: a systematic review.

OBJECTIVE: This systematic review aimed to establish the evidence behind the use of pre-operative calcium, vitamin D or both calcium and vitamin D to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy. METHOD: This review included prospective clinical trials on adult human patients that were published in English and which studied the effects of pre-operative supplementation with calcium, vitamin D or both calcium and vitamin D on the rate of post-operative hypocalcaemia following total thyroidectomy. RESULTS: Seven out of the nine trials included reported statistically significantly reduced rates of post-operative laboratory hypocalcaemia (absolute risk reduction, 13-59 per cent) and symptomatic hypocalcaemia (absolute reduction, 11-40 per cent) following pre-operative supplementation. CONCLUSION: Pre-operative treatment with calcium, vitamin D or both calcium and vitamin D reduces the risk of post-operative hypocalcaemia and should be considered in patients undergoing total thyroidectomy.

Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis.

[Figure: see text].

Switching from conventional therapy to burosumab injection has the potential to prevent nephrocalcinosis in patients with X-linked hypophosphatemic rickets.

OBJECTIVES: X-linked hypophosphatemic rickets (XLH) is a congenital fibroblast growth factor (FGF)23-related metabolic bone disease that is treated with active vitamin D and phosphate as conventional therapies. Complications of these therapies include nephrocalcinosis (NC) caused by excessive urine calcium and phosphate concentrations. Recently, an anti-FGF23 antibody, burosumab, was developed and reported to be effective in poorly-controlled or severe XLH patients. This study aimed to reveal the impact of switching treatments in relatively well-controlled XLH children with the Rickets Severity Scale less than 2.0. METHODS: The effects of the two treatments in eight relatively well-controlled XLH children with a mean age of 10.4 ± 1.9 years were compared retrospectively for the same treatment duration (31 ± 11 months) before and after the baseline. RESULTS: Actual doses of alfacalcidol and phosphate as conventional therapy were 150.9 ± 43.9 ng/kg and 27.5 ± 6.3 mg/kg per day, respectively. Renal echography revealed spotty NC in 8/8 patients, but no aggravation of NC was detected by switching treatments. Switching treatments increased TmP/GFR (p=0.002) and %TRP (p<0.001), and improved the high urine calcium/creatinine ratio to the normal range (p<0.001) although both treatments controlled disease markers equally. Additionally, low intact parathyroid hormone during conventional therapy was increased within the normal range by switching treatments. CONCLUSIONS: Our results suggest that a high dose of alfacalcidol was needed to control the disease, but it caused hypercalciuria and NC. We concluded that switching treatments in relatively well-controlled XLH children improved renal phosphate reabsorption and decreased urine calcium extraction, and may have the potential to prevent NC.

Alfacalcidol improves the growth velocity in children with vitamin D deficiency/insufficiency: A single center retrospective cohort study.

OBJECTIVES: To investigate the growth velocity-improving effects of vitamin D replacement therapy in pediatric patients diagnosed with vitamin D deficiency and insufficiency. STUDY DESIGN: A retrospective cohort study was conducted in 34 pediatric patients diagnosed with vitamin D deficiency/insufficiency. Based on the clinical findings, the subjects were divided into two groups: a bowed leg (BL) group and a non-bowed leg (non-BL) group. After the initiation of alfacalcidol, the standard deviation score (SDS) of their heights, weights and growth velocities in each group were monitored. RESULTS: The median age at the first visit was significantly lesser in the BL group (1.58 years old [interquartile range (IQR): 1.33, 2.17]) than that in the non-BL group (3.00 years old [IQR: 2.33, 3.67]). On the contrary, the SDS for height was significantly lower in the non-BL group (-2.27 [IQR: -2.63, -1.94]) than that in the BL group (-1.37 [IQR: -1.91, -1.07]). One-year treatment with alfacalcidol showed significant improvements in both height SDSs and growth velocity SDSs not only in the BL group but also in the non-BL group. CONCLUSIONS: The current study revealed that vitamin D replacement therapy improved the growth rate in children with vitamin D deficiency/insufficiency, regardless of the presence of BL. This study emphasizes the importance of assessing the vitamin D status in children with poor growth rates and suggests that alfacalcidol could be a valid option for the treatment of short stature.

Alfacalcidol vs Calcitriol in the Management of Patient With Hypoparathyroidism: A Randomized Controlled Trial.

CONTEXT: Alfacalcidol and calcitriol are commonly used for managing hypoparathyroidism. Their relative merits have not been systematically assessed. OBJECTIVE: We compared the effect of alfacalcidol and calcitriol on phosphatemic control, hypercalciuria, and associated factors in idiopathic-hypoparathyroidism (IH). DESIGN AND SETTING: Open-label randomized controlled trial, tertiary care center. SUBJECTS AND METHODS: IH patients with optimal calcemic control on alfacalcidol were continued on the same (n = 20) or switched to calcitriol (n = 25) at half of the ongoing alfacalcidol dose. The dose was adjusted during follow-up to maintain serum total calcium between 8.0 and 9.5 mg/dL. Serum calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24-h urine calcium-to-creatinine ratio, and fractional excretion of phosphorus (FEPh) were measured at baseline and 6 months. Plasma intact-FGF23 was measured at final follow-up. RESULT: Patients receiving alfacalcidol and calcitriol had comparable serum calcium at 6 months (8.7 ±â€…0.4 vs 8.9 ±â€…0.4 mg/dL, P = 0.13). Their median [interquartile range (IQR)] dose at 6 months was 2.0 (1.0-2.5) and 0.75 (0.5-1.0) µg/d, respectively. Serum 1,25(OH)2D levels were physiological in both (35.3 ±â€…11.6 and 32.3 ±â€…16.9 pg/mL). Serum phosphate and calcium excretion were comparable in 2 arms. A majority had hyperphosphatemia (75% vs 76%), hypercalciuria (75% vs 72%), and elevated FGF23 (116 ±â€…68 and 113 ±â€…57 pg/mL). Age showed significant independent association with plasma FGF23 (ß = 1.9, P = 0.001). Average FEPh was low despite high FGF23. CONCLUSION: At optimal calcium control, both alfacalcidol and calcitriol lead to comparable but high serum phosphate levels, hypercalciuria, physiological circulating 1,25(OH)2D, and elevated FGF23. Further studies are required to systematically investigate other treatment options.

Evaluation of the potential anticancer activity of different vitamin D metabolites on colorectal and breast cancer cell lines.

OBJECTIVES: Vitamin D is very important for calcium and mineral metabolism, and many hypotheses appear to link sunlight exposure with cancer risk and prognosis. As many studies supported the antitumor effect of vitamin D we wanted to investigate the potential effect of multiple vitamin D metabolites. METHODS: This study compared the anticancer effect of three inactive forms of vitamin D3 which are; cholecalciferol, alfacalcidol, and calcifediol on two human cancer cell lines colorectal cancer (CaCo II) and breast cancer (MCF-7). All were examined after 24, 48, and 72 h continuous exposure using a colorimetric assay (MTT) seeded in 96-multiwell plates. Doxorubicin anticancer used as a standard agent for comparison, while normal skin fibroblast cells (HDFa) was used as our negative control. IC50 values were calculated as indication of antitumor effect. RESULTS: Broad-spectrum of cytotoxicity with IC50 values ranging from 4 to 200 µM were found. Alfacalcidol was the most potent cytotoxic agents on colorectal cancer (CaCo II) and breast cancer (MCF-7) compared to cholecalciferol, and calcifediol. Both, alfacalcidol and calcifediol were more cytotoxic than cholecalciferol on the tested cell lines as they are partially active metabolites. Breast cancer (MCF-7) was the most sensitive to all metabolites at all-time intervals with the best IC50 values of 4.35 µM ± 1.06 after 72 h continuous exposure of alfacalcidol. CONCLUSIONS: Vitamin D metabolites are a potential option for cancer treatment along with or an alternative to chemo-therapeutics although extensive preclinical studies are required to prove this effect.

Impact of bone mineral density in reducing fracture risk in patients receiving alendronate plus alfacalcidol therapy.

BACKGROUD: Changes in bone mineral density (BMD) are a potential surrogate marker for fracture endpoints in clinical trials. However little is known whether the increase in BMD in response to combination treatment with alendronate plus alfacalcidol is associated with fracture risk reduction. We aimed to evaluate the impact of BMD on fracture risk in osteoporosis patients, using the data from the randomized clinical trial comparing alendronate plus alfacalcidol with alendronate alone. METHODS: We selected 412 patients with two or more prevalent vertebral fractures and who had BMD measurements at baseline and after 6, 12, and/or 24 months out of 2022 patients from the database of the Japanese Osteoporosis Intervention Trial. Patients in this subset who received combination treatment with alendronate plus alfacalcidol had shown a lower risk of fracture than patients treated with alendronate alone. We used Poisson regression model analysis to calculate the proportion of treatment effect (PTE) that was attributable to BMD increases in patients receiving combination treatment. RESULTS: The highest PTE attributable to changes in BMD was 1.2% in patients with a BMD increase of 3% or more in the lumbar spine. For BMD measurements of the radius, the highest PTE was 2.8% with a BMD increase of 0% or more. For BMD measurements of the metacarpal bone, the highest PTE was 1.2% with a BMD increase of 3% or more. In patients with a BMD greater than or equal to 70% of the young adult mean in the lumbar spine, the PTE attributable to BMD was 0.2%. In patients with a BMD greater than or equal to 70% of the young adult mean in the radius, the PTE attributable to BMD was 0.3%. CONCLUSIONS: The additional effects of alfacalcidol in reducing fracture risk do not likely result from increased BMD; other mechanisms remain a possibility.