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.

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.

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.

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 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.

Short-term Effects of Alfacalcidol on Hospital Length of Stay in Patients Undergoing Valve Replacement Surgery: A Randomized Clinical Trial.

PURPOSE: Vitamin D deficiency is highly prevalent in critically ill patients, and has been associated with more prolonged length of hospital stay and poor prognosis. Patients undergoing open-heart surgery are at higher risk due to the associated life-threatening postoperative complications. This study investigated the effect of alfacalcidol treatment on the length of hospital stay in patients undergoing valve-replacement surgery. METHODS: This single-center, randomized, open-label, controlled trial was conducted at El-Demerdash Cardiac Academy Hospital (Cairo, Egypt), from April 2017 to January 2018. This study included adult patients undergoing valve-replacement surgery who were randomized to the intervention group (n = 47; alfacalcidol 2 µg/d started 48 h before surgery and continued throughout the hospital stay) or to the control group (n = 42). The primary end points were lengths of stay (LOS) in the intensive care unit (ICU) and in the hospital. Secondary end points were the prevalence of postoperative hospital-acquired infections, cardiac complications, and in-hospital mortality. FINDINGS: A total of 86 patients were included in the final analysis, with 51 (59.3%) being vitamin D deficient on hospital admission. Treatment with alfacalcidol was associated with a statistically significant decrease in ICU LOS (hazard ratio = 1.61; 95% CI, 1.77-2.81; P = 0.041) and hospital LOS (hazard ratio = 1.63; 95% CI, 1.04-2.55; P = 0.034). Treated patients had a significantly lower postoperative infection rate than did the control group (35.5% vs 56.1%; P = 0.017). The median epinephrine dose was lower in the intervention group compared to that in the control group (5.9 vs 8.2 mg; P = 0.019). The rate of in-hospital mortality was not significantly different between the 2 groups. IMPLICATIONS: Early treatment with 2 µg of alfacalcidol in patients undergoing valve-replacement surgery is promising and well tolerated. This effect may be attributed to its immunomodulatory and cardioprotective mechanisms. ClinicalTrials.gov identifier: NCT04085770.

The first case report of Kyphoscoliotic Ehlers-Danlos syndrome of chinese origin with a novel PLOD1 gene mutation.

BACKGROUND: Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by progressive kyphoscoliosis, congenital muscular hypotonia, marked joint hypermobility, and severe skin hyperextensibility and fragility. Deficiency of lysyl hydroxylase 1 (LH1) due to mutations of PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) gene has been identified as the pathogenic cause of kEDS (kEDS-PLOD1). Up to now, kEDS-PLOD1 has not been reported among Chinese population. CASE PRESENTATION: A 17-year-old Chinese male patient presenting with hypotonia, joint hypermobility and scoliosis was referred to our hospital. After birth, he was found to have severe hypotonia leading to delayed motor development. Subsequently, joint hypermobility, kyphoscoliosis and amblyopia were found. Inguinal hernia was found at age 5 years and closed by surgery. At the same time, he presented with hyperextensible and bruisable velvety skin with widened atrophic scarring after minor trauma. Dislocation of elbow joint was noted at age of 6 years. Orthopedic surgery for correction of kyphoscoliosis was performed at age 10 years. His family history was unremarkable. Physical examination revealed elevated blood pressure. Slight facial dysmorphologies including high palate, epicanthal folds, and down-slanting palpebral fissures were found. He also had blue sclerae with normal hearing. X-rays revealed severe degree of scoliosis and osteopenia. The Echocardiography findings were normal. Laboratory examination revealed a slightly elevated bone turnover. Based on the clinical manifestations presented by our patient, kEDS was suspected. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G > A, p.C566Y), confirming the diagnosis of kEDS-PLOD1. The patient was treated with alfacalcidol and nifedipine. Improved physical strength and normal blood pressure were reported after 12-month follow-up. CONCLUSIONS: This is the first case of kEDS-PLOD1 of Chinese origin. We identified one novel mutation of PLOD1, extending the mutation spectrum of PLOD1. Diagnosis of kEDS-PLOD1 should be considered in patients with congenital hypotonia, progressive kyphoscoliosis, joint hypermobility, and skin hyperextensibility and confirmed by mutation analysis of PLOD1.

Fall Prevention and Anti-Osteoporosis in Osteopenia Patients of 80 Years of Age and Older: A Randomized Controlled Study.

To evaluate the effects of two fall-prevention and anti-osteoporotic protocols in elderly patients with osteopenia (OPA). METHODS: The present randomized controlled study included patients with OPA (n =123). The age of these patients was ≥80 years old, with the mean age of 83.54 ± 2.99 years, and the male-to-female ratio was 2.97:1.00. Fall-prevention guidance was given to all patients. Patients in the experiment group (n = 62) orally received 600 mg/d of calcium carbonate, 0.5 µg/d of alfacalcidol, and 70 mg/week of alendronate, while patients in the control group (n = 61) orally received 600 mg/d of calcium carbonate and 0.5 µg/d of alfacalcidol for 18 months. The grip strength, gait speed, bone turnover markers, serum calcium, serum phosphorus, parathyroid hormone (PTH), and bone mineral density were measured, and the Timed Up and Go (TUG) test and the chair rising test (CRT) were performed. Falls, fragility fractures, medication compliance, and side effects of the drugs were recorded. RESULTS: The serum levels of bone turnover markers (type I procollagen amino-terminal peptide [P1NP], type I collagen carboxyl terminal peptide [ß-CTx], and osteocalcin [OC]) decreased, while the bone mineral density of the lumbar spine and bilateral femoral neck increased after treatment in the experiment group (P < 0.05, P < 0.01). The rate of change in bone mineral density of the bilateral femoral neck was higher in the experiment group than the control group (3.43% vs 0.03%, P < 0.05; 2.86% vs -0.02%, P < 0.01). After treatment, the proportion of patients with increased hip T scores in the experiment group (66.1%, 41/62) was significantly higher than the proportion (35.0%, 21/60) in the control group (P = 0.001). The incidence of fall decreased in both groups after treatment compared to that before treatment (54.8% vs 33.9% and 54.1% vs 36.7%, respectively; P < 0.05). The incidence of fragility fractures was lower in the experiment group than the control group (8.1% vs 20.0%, P = 0.057). During the intervention period, the incidence of fragility fractures in patients who did not fall (3.8%, 3/79) was significantly lower than that in patients who fell (32.6%, 14/43) (P = 0.000). The risk of fragility fractures was significantly lower in patients who did not fall compared to patients who fell (relative risk: 0.117, 95% confidence interval: 0.035-0.384). CONCLUSION: The combination of alendronate sodium with alfacalcidol and calcium can significantly improve the bone mineral density of the lumbar spine and femoral neck. For older patients with OPA, subjectively paying attention to avoiding falls can significantly reduce the risk of fragility fractures.

Effects of parathyroid hormone and vitamin D supplementation on stroke among patients receiving peritoneal dialysis.

BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) patients have a high incidence of stroke and commonly have increased parathyroid hormone levels and vitamin D insufficiency. We seek to investigate the incidence of stroke and the role of parathyroid hormone and vitamin D supplementation in stroke risk among CAPD patients. METHODS: This study employed a retrospective design. We enrolled a Chinese cohort of 980 CAPD patients who were routinely followed in our department. The demographic and clinical data were recorded at the time of initial CAPD and during follow-up. The included patients were separated into non-stroke and stroke groups. The effects of parathyroid hormone and vitamin D supplementation on stroke in CAPD patients was evaluated. The primary endpoint is defined as the first occurrence of stroke, and composite endpoint events are defined as death or switch to hemodialysis during follow-up. RESULTS: A total of 757 eligible CAPD patients with a mean follow-up time of 54.7 (standard deviation, 33) months were included in the study. The median incidence of stroke among our CAPD patients was 18.9 (interquartile range, 15.7-22.1) per 1000 person-years. A significant nonlinear correlation between baseline iPTH and hazard of stroke (p-value of linear association = 0.2 and nonlinear association = 0.002) was observed in our univariate Cox regression analysis, and low baseline iPTH levels (≤150 pg/ml) were associated with an increased cumulative hazard of stroke. Multivariate Cox regression analysis indicated a significant interaction effect between age and iPTH after adjusting for other confounders. Vitamin D supplementation during follow-up was a predictive factor for stroke in our cohort. CONCLUSIONS: CAPD patients suffered a high risk of stroke, and lower iPTH levels were significantly correlated with an increased risk of stroke. Nevertheless, vitamin D supplementation may reduce the risk of stroke in these patients.

Eldecalcitol is superior to alfacalcidol in maintaining bone mineral density in glucocorticoid-induced osteoporosis patients (e-GLORIA).

INTRODUCTION: Eldecalcitol 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 METHODS: A 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. RESULTS: Lumbar 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. CONCLUSIONS: Eldecalcitol 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 NUMBER: UMIN000011700.

Minodronate combined with alfacalcidol versus alfacalcidol alone for glucocorticoid-induced osteoporosis: a multicenter, randomized, comparative study.

INTRODUCTION: This 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 METHODS: The 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. RESULTS: Of 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. CONCLUSIONS: Minodronate 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.

Nutraceutical Augmentation Strategies for Depression: A Narrative Review.

Context: Depression is one of the most commonly diagnosed psychiatric disorders, but antidepressant pharmacotherapy often fails to achieve remission, leading health care professionals and researchers to consider various augmentation strategies to improve clinical outcomes. Objective: To assess the safety, tolerability, and efficacy of nutraceutical augmentation for depression. Methods: Nutraceutical-focused systematic reviews and clinical practice guidelines identified the more commonly studied augmentation strategies for depression. Results: S-adenosylmethionine, l-methylfolate, omega-3 fatty acids, and hydroxyvitamin D have sufficient scientific evidence to support their clinical consideration in the stepped care approach to the management of depression. Conclusions: Clinical remission is the goal in the management of depression, and nutraceuticals may be part of an overall treatment approach to achieve that outcome.

Prescribing and adherence to bone protection medications following hip fracture in the United Kingdom: results from the World Hip Trauma Evaluation (WHiTE) cohort study.

AIMS: Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. PATIENTS AND METHODS: The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants' discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery. RESULTS: Of 5456 recruited patients with baseline data, 2853 patients (52%) were prescribed bone protection medication at discharge, of which oral bisphosphonates were the most common, 4109 patients (75%) were prescribed vitamin D or calcium, and 606 patients (11%) were not prescribed anything. Of those prescribed a bone protection medication, only 932 patients (33%) reported still taking their medication 120 days later. CONCLUSION: These data provide a reference for current prescription and adherence rates. Adherence with oral medication remains poor in patients with hip fracture. Cite this article: Bone Joint J 2019;101-B:1402-1407.

Potentially repurposable drugs for schizophrenia identified from its interactome.

We previously presented the protein-protein interaction network of schizophrenia associated genes, and from it, the drug-protein interactome which showed the drugs that target any of the proteins in the interactome. Here, we studied these drugs further to identify whether any of them may potentially be repurposable for schizophrenia. In schizophrenia, gene expression has been described as a measurable aspect of the disease reflecting the action of risk genes. We studied each of the drugs from the interactome using the BaseSpace Correlation Engine, and shortlisted those that had a negative correlation with differential gene expression of schizophrenia. This analysis resulted in 12 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for schizophrenia (disorder versus normal). Some of these drugs were already being tested for their clinical activity in schizophrenia and other neuropsychiatric disorders. Several proteins in the protein interactome of the targets of several of these drugs were associated with various neuropsychiatric disorders. The network of genes with opposite drug-induced versus schizophrenia-associated expression profiles were significantly enriched in pathways relevant to schizophrenia etiology and GWAS genes associated with traits or diseases that had a pathophysiological overlap with schizophrenia. Drugs that targeted the same genes as the shortlisted drugs, have also demonstrated clinical activity in schizophrenia and other related disorders. This integrated computational analysis will help translate insights from the schizophrenia drug-protein interactome to clinical research - an important step, especially in the field of psychiatric drug development which faces a high failure rate.

Successful management of tertiary hyperparathyroidism associated with hypophosphataemic rickets in an adult.

Tertiary hyperparathyroidism (THP) is a rare complication in patients with hypophosphataemic rickets (HR), usually related to long-term management with active vitamin D analogues and oral phosphate salts. If left untreated, THP may aggravate bone and renal disease. We report a case of THP, which developed during the course of HR. Preoperatively, cinacalcet administration along with gradual increase in alphacalcidol dose, led to almost normalization of serum calcium and decrease in parathyroid hormone (PTH) concentrations. The patient underwent an uneventful subtotal parathyroidectomy, resulting in PTH normalization and stabilization of eucalcaemia during 18 months of follow-up. We conclude that, except for optimal dosage of elementary phosphate and alphacalcidol, cinacalcet prior to parathyroidectomy may be an effective option in patients with HR complicated with THP.