The response of elderly veterans to daily vitamin D3 supplementation of 2,000 IU: a pilot efficacy study

OBJECTIVES: To determine the prevalence of hypovitaminosis D (serum 25‐hydroxyvitamin D<32 ng/mL; HVD) in a population of elderly veterans and conduct a preliminary assessment of the efficacy of supplementation with cholecalciferol in correcting HVD. DESIGN: Randomized, double‐blind, placebo‐controlled clinical trial. SETTING: Geriatric clinic at the Bruce W. Carter Veterans Affairs Medical Center, Miami, Florida. PARTICIPANTS: Veterans aged 70 and older. INTERVENTION: Oral cholecalciferol 2,000 IU daily or placebo for 6 months. MEASUREMENTS: Serum calcium, 25‐hydroxyvitamin D, parathyroid hormone, and 24‐hour urinary calcium. RESULTS: Of the 34 participants who completed the study, 62% had HVD at baseline. In the treatment group, mean serum 25‐hydroxyvitamin D level rose from 28.4±7.9 ng/mL at baseline to 42.7±10.5 ng/mL at the end of the trial, but levels remained less than 32 ng/mL in three of 17 (18%) of the participants. In the placebo group, the baseline level of 27.7±8.3 ng/mL remained unchanged (28.8±8.7 ng/mL). Supplementation did not alter serum or urinary calcium levels and did not result in any adverse events. CONCLUSION: These initial observations suggest that, in older veterans, cholecalciferol 2,000 IU daily for 6 months is generally safe and corrects HVD in most but not all individuals.     

Heterogeneity in Serum 25‐Hydroxy‐Vitamin D Response to Cholecalciferol in Elderly Women with Secondary Hyperparathyroidism and Vitamin D Deficiency

OBJECTIVES: To compare the effects on parathyroid hormone (PTH) and 25‐hydroxy‐vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. DESIGN: Randomized‐controlled trial with 6‐month follow‐up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Sixty community‐dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. INTERVENTION: Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D₃ group) or cholecalciferol 1,000 IU/day (daily D₃ group). MEASUREMENTS: Serum PTH, 25(OH)D, calcium, bone‐specific alkaline phosphatase, β‐C‐terminal telopeptide of type I collagen, phosphate, 24‐hour urinary calcium excretion. RESULTS: The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D<20 ng/mL)], and 36 subjects (60%) had severe deficiency (<10 ng/mL), with no difference between the groups (severe deficiency: intermittent D₃ group, n=18; daily D₃ group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase±standard deviation of 25(OH)D at 6 months was higher in the intermittent D₃ group (22.7±11.8 ng/mL) than in the daily D₃ group (13.7±6.7 ng/mL, P<.001), with a higher proportion of participants in the intermittent D₃ group reaching desirable serum concentration of 25(OH)D ≥ 30 ng/mL (55% in the intermittent D₃ group vs 20% in the daily D₃ group, P<.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. CONCLUSION: Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher‐dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet‐higher doses will be required for adequate vitamin D repletion.     

ORIGINAL ARTICLE: Association between 25‐hydroxyvitamin D,somatic muscle weakness and falls risk in end‐stage renal failure

Objective Suboptimal levels of 25‐hydroxyvitamin D (25OHD) are common in haemodialysis patients (Chronic Kidney disease‐5D: CKD‐5D) and may be associated with reduced muscle strength and increased falls risk. We tested the hypothesis that 25OHD levels may be independently associated with falls risk in CKD‐5D. Background Supplementation with calcium and cholecalciferol reduces hip and other nonvertebral fractures in elderly individuals, and this effect may in part be attributable to reduction in falls frequency. The relationship between 25OHD and falls risk has not been investigated in CKD‐5D. Design and Patients This is a cross‐sectional study of 25 CKD‐5D patients with predialysis 25OHD, 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and intact parathyroid hormone (iPTH) measurement. Falls risk was assessed by quadriceps muscle strength, FallsScreen^© test (FST), Berg Balance Scale (BBS), timed ‘up and go’ (TUG) test, Modified Barthel Index (MBI) and Falls Efficacy Scale (FES). Results Mean age was 69·8 ± 12·1 years, and median time on dialysis was 3·1 years. Median 25OHD level was 55·3 nmol/l (range 20·8–125·8 nmol/l). Muscle strength was significantly positively correlated with 25OHD (P = 0·024) but not with 1,25(OH)₂D (P = 0·477) or PTH (P = 0·461). Statistically significant correlation between 25OHD levels and FST (P = 0·028) plus MBI (P = 0·0046) was noted. No significant correlation was detected between falls risk and 1,25(OH)₂D or PTH. Conclusions Suboptimal levels of 25OHD in CKD‐5D are associated with reduced quadriceps muscle strength and increased falls risk. 25OHD may be more important than the active renal metabolite 1,25(OH)₂D for muscle strength with implications for vitamin D choice and goals of supplementation. Further investigation is required to examine effectiveness of calciferol supplementation on the incidence of falls in CKD‐5D.     

Efficacy of risedronate with cholecalciferol on 25-hydroxyvitamin D level and bone turnover in Korean patients with osteoporosis

Background We performed a randomized, double‐blind, prospective, 16‐week clinical trial to evaluate the efficacy and safety of risedronate with and without cholecalciferol on 25‐hydroxyvitamin D [25(OH)D] levels and bone markers in Korean patients with osteoporosis. Methods We randomly assigned 164 adults with osteoporosis to one of two treatment groups: weekly risedronate 35 mg and cholecalciferol 5600 IU combined in a single pill (RSD+) or weekly risedronate 35 mg alone (RSD). We measured serum levels of 25(OH)D, parathyroid hormone (PTH), and bone markers and performed muscle function tests, at baseline and after 16 weeks of treatment. Results After 16 weeks of treatment, mean serum 25(OH)D increased significantly from 39·8 to 70·8 nmol/l in the RSD+ group and declined significantly from 40·5 to 35 nmol/l in the RSD group. Although both treatment groups had significant increases in serum PTH over baseline during the study, the RSD group had a significantly larger increase than the RSD+ group (13·6 vs 4·8 ng/l; P = 0·0005). In both groups, serum bone‐specific alkaline phosphatase (BSAP) and C‐terminal telopeptide (CTX) declined rapidly; there were no significant differences between groups. There was also no significant difference between groups in lower‐extremity function tests. The overall incidence of clinical adverse events was not significantly different between groups. Conclusion In patients with osteoporosis, a once‐weekly pill of risedronate and cholecalciferol provided equivalent antiresorptive efficacy to risedronate alone in terms of bone turnover and improved 25(OH)D level over a 16‐week treatment period without significant adverse events.     

Vitamin D status, physical performance and body mass in patients surgically cured for primary hyperparathyroidism compared with healthy controls - a cross-sectional study

Objective Low plasma 25‐hydroxyvitaminD (25OHD) levels, reduced muscle strength and increased body mass index (BMI) are well‐known characteristics of primary hyperparathyroidism (PHPT). Mechanisms for low 25OHD levels, increased BMI and potential changes after parathyroidectomy are unknown. Muscle strength is reported to increase following surgical cure, but whether the improvement corresponds to healthy controls’ performances remains largely unknown. Patients We studied 51 patients with former PHPT [mean age 61(36–77) years] successfully treated by surgery [mean time since operation 7·4(5–15) years] and 51 sex‐ and age‐matched controls. Measurements Physical performance include “repeated chair stand” (RCS), “timed up and go” (TUG), muscle strength [hand grip, elbow flexion/extension and knee flexion/extension (60°/90°)], postural stability, biochemistry and anthropometric indices. Results Forty‐one cases had pathologically verified adenoma, three had hyperplasia and three had uncertain diagnosis whereas four had missing data. Dietary calcium intake, vitamin D supplementation and biochemistry including PTH and 25OHD levels did not differ between groups. Former patients had significantly higher BMI (28·8 ± 6·0 kg/m²) than controls (26·0 ± 4·7kg/m²). Muscle pain was more frequently reported by cases than controls, and cases performed RCS slower than controls (P = 0·02). Furthermore, female cases had lower muscle strength in knee flexion 60° (P = 0·02) and 90° (P = 0·05). Former patients no longer differed from controls after adjustment for BMI. Conclusion Following cure, 25OHD levels are normalized suggesting 25OHD insufficiency is not a constitutional characteristics in patients with PHPT. Increased BMI seems to be sustained. Whether this is caused by decreased muscle strength or reduced muscular performance causes adiposity needs further investigations.     

Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults*

OBJECTIVES The physiological role Of growth hormone in adult life has recently attracted increased Interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH In a large number of hypopituitary adults. DESIGN A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH dally dose was 0·04 (0·02-0·05) IU/kg s.c. PATIENTS Forty GH deficient hypopituitary patients (19 M, 21 F; aged 19–67 years) on conventional replacement therapy were studied. MEASUREMENTS Serum insulin like growth factor I (IGF-I), skinfold thickness, total body potassium, total body water (TBW), exercise tolerance and muscle strength, and well-being. RESULTS During the 6-month double blind phase, two GH treated patients withdrew because of adverse events. Lean body mass (LBM) increased and percentage body fat (%BF) decreased on GH but not on placebo (P) (LBM: (GH: from 48·5 ± 9·6 to 49·6 ± 9·5kg; P: from 50·9 ± 9·2 to 50·1 ± 9·0kg, P < 0·05 GH vs P) and TBW (OH: from 34·7 ± 11·4 to 34·2 ± 10·7; P: from 37·4 ± 7·6 to 38·7 ± 8·1, P < 0·05 GH vs P). TBW Increased on GH (P < 0·01) but not on P. No change was observed In waist-to-hip ratio or in muscle strength. During longer-term follow-up combining the double blind and open phase components of the study, 34, 27 and 11 patients received OH for 6,12 and 18 months respectively. Patients dropped out because of adverse events or lack of perceived benefit. Skinfold thicknesses decreased significantly at 6 and 12 months and the waist circumference at 6 months. Waist-to-hip ratio decreased significantly on OH at 12 months. LBM increased on GH treatment from 49·6 ± 9·1 to 51·6 ± 9·4kg (P < 0·0006), 51·9 ± 8·9kg (P < 0·07) and 53·1 ± 10·5 kg (P < 0·0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37·2 ± 10·7 to 34·7 ± 10·1 (P < 0·005), 35·1 ± 12·8 (NS) and 34·5 ± 86 (P < 0·04) at 6, 12 and 18 months respectively. TBW also increased at 6 and 12 months of GH treatment. Exercise time increased significantly at 6, 12 and 18 months of GH treatment. Muscle strength in selected muscle groups Increased significantly at 6, 12 or 18 months of GH treatment. Randomization resulted in the placebo group having a greater GHQ score (higher morbidity) than the OH group before therapy. Over the controlled phase, GHQ scores improved on placebo but not on OH and CPRS score was unchanged in either group. In the open phase, the GHQ score did not change on GH therapy but CPRS score improved at 6 and 12 months. CONCLUSIONS Growth hormone replacement therapy in adults for 6 months increased lean body mass, total body water and exercise tolerance, and decreased body fat. Growth hormone replacement for longer than 6 months maintains the advantageous effects seen in shorter-term studies and may have additional effects on body fat distribution, muscle strength and psychological well-being.     

A prospective study of the associations between 25‐hydroxy‐vitamin D,sarcopenia progression and physical activity in older adults

Objective Low 25‐hydroxyvitamin D (25OHD) levels may be associated with both sarcopenia (the age‐related decline in muscle mass and function) and low physical activity (PA). Our objective was to describe prospective associations between 25OHD, muscle parameters, and PA in community‐dwelling older adults. Design Prospective, population‐based study with a mean follow‐up of 2·6 ± 0·4 years. Patients Six hundred and eighty‐six community‐dwelling older adults (49% women; mean ± SD 62 ± 7 years old). Measurements Appendicular lean mass percentage (%ALM) and body fat assessed by Dual‐energy X‐ray Absorptiometry, leg strength by dynamometer, leg muscle quality (LMQ), PA assessed by pedometer, self‐reported sun exposure by questionnaire, and serum 25OHD measured by radioimmunoassay. Results Participants with 25OHD ≤50 nm had lower mean %ALM, leg strength, LMQ and PA (all P < 0·05). As a continuous function, baseline 25OHD was a positive independent predictor of change in leg strength (β = 5·74 kg, 95% CI 0·65, 10·82) and LMQ (β = 0·49 kg/kg, 95% CI 0·17, 0·82). Also, change in 25OHD was positively predicted by baseline %ALM (β = 2·03 pm /p.a., 95% CI 0·44, 3·62) leg strength (β = 0·30 pm /p.a., 95% CI 0·06, 0·53), LMQ (β = 4·48 pm /p.a., 95% CI 0·36, 8·61) and PA (β = 2·63 pm /p.a., 95% CI 0·35, 4·92) after adjustment for sun exposure and body fat. Conclusions 25OHD may be important for the maintenance of muscle function, and higher skeletal muscle mass and function as well as general PA levels may also be beneficial for 25OHD status, in community‐dwelling older adults.     

A randomized controlled trial of the effects of vitamin D on muscle strength and mobility in older women with vitamin D insufficiency

OBJECTIVES: To evaluate the effects of vitamin D treatment on muscle strength and mobility in older women with vitamin D insufficiency. DESIGN: One‐year population‐based, double‐blind, randomized, controlled trial. SETTING: Perth, Australia (latitude 32°S). PARTICIPANTS: Three hundred two community‐dwelling ambulant elderly women aged 70 to 90 with a serum 25‐hydroxyvitamin D (25(OH)D) concentration less than 24 ng/mL. INTERVENTION: Vitamin D₂ 1,000 IU/d or identical placebo; calcium citrate (1 g calcium/d) in both groups. MEASUREMENTS: Lower limb muscle strength and mobility as assessed using the Timed Up and Go Test (TUAG). RESULTS: At baseline, mean±standard deviation serum 25(OH)D was 17.7±4.2 ng/mL; this increased to 24.0±5.6 ng/mL in the vitamin D group after 1 year but remained the same in the placebo group. For hip extensor and adductor strength and TUAG, but not for other muscle groups, a significant interaction between treatment group and baseline values was noted. In those with baseline values in the lowest tertile, vitamin D improved muscle strength and TUAG more than calcium alone (mean (standard error): hip extensors 22.6% (9.5%); hip adductors 13.5% (6.7%), TUAG 17.5% (7.6%), P<.05). Baseline 25(OH)D levels did not influence patient response to supplementation. CONCLUSION: Vitamin D therapy was observed to increase muscle function in those who were the weakest and slowest at baseline. Vitamin D should be given to people with insufficiency or deficiency to improve muscle strength and mobility.     

High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study

We report results of a pilot study of high‐dose vitamin D in sickle cell disease (SCD). Subjects were given a 6‐week course of oral high‐dose cholecalciferol (4000–100 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82·5% and 52·5% of subjects, respectively. Subjects who received high‐dose vitamin D achieved higher serum 25‐hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality‐of‐life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.     

Discrepant influence of vitamin D status on parathyroid hormone and bone mass after two years of calcium supplementation

Objective To investigate the influence of vitamin D status on parathyroid hormone and bone mass after a 2‐year supplementation of calcium alone. Patients and Methods Randomized, double‐blind, placebo‐controlled clinical trial, in healthy postmenopausal women without osteoporosis: three hundred and thirty‐six subjects aged 60–97 years were studied and randomized to receive elemental calcium 500 mg/day (n = 175) or placebo (n = 161) for 2 years. Measurements Changes in parathyroid hormone (PTH) and bone mineral density (BMD) from baseline and vitamin D status. Values are presented as means ± SD. Results After 2 years, subjects with calcium supplementation had significant decrease in plasma PTH level (4·4 ± 1·7 vs 4·7 ± 1·9 pmol/l, P < 0·01), improved lumbar BMD (1·031 ± 0·12 vs 1·004 ± 0·12 g/cm², P < 0·001) and total hip BMD (0·890 ± 0·10 vs 0·883 ± 0·10 g/cm², P < 0·001) without change in femoral neck BMD. In the placebo group, PTH level significantly increased (4·8 ± 1·6 vs 4·5 ± 1·5 pmol/l, P < 0·001), lumbar BMD slightly increased (1·027 ± 0·14 vs 1·018 ± 0·14 g/cm², P < 0·001), total hip and femoral neck BMD decreased (0·876 ± 0·11 vs 0·887 ± 0·11 g/cm², P < 0·001 and 0·783 ± 0·10 vs 0·798 ± 0·10 g/cm², P < 0·001, respectively). When subjects were classified according to baseline 25‐hydroxyvitamin D [25(OH)D] levels into those with 25(OH)D in the lower tertile (lowVitD) and those in the middle and upper tertiles combined (normVitD). The degree of PTH suppression after calcium supplementation was significantly higher in the normVitD compared to the lowVitD groups (?5·6 ± 26·7%vs 1·3 ± 27·2%, P < 0·05). No effect of vitamin D status on the change in lumbar BMD after calcium supplementation was demonstrated. Despite the higher suppression of PTH, there was a slight decrease in femoral neck BMD after calcium supplementation in the normVitD group while femoral neck BMD was more or less maintained in the lowVitD group (?0·6 ± 3·2%vs 0·5 ± 2·9%, P < 0·05). Conclusion Calcium supplementation appears to affect femoral bone mass less in Thai postmenopausal women with adequate vitamin D status, despite higher suppression of PTH.     

Durability of the effects of testosterone and growth hormone supplementation in older community‐dwelling men: the HORMA Trial

Objectives To determine the durability of anabolic effects and adverse events (AEs) after stopping testosterone and growth hormone supplementation in older men. Design Secondary analysis of a double‐masked, randomized controlled trial of testosterone gel (5 or 10 g/daily) plus rhGH (0, 3 or 5 μg/kg/day) with follow‐up of outcomes 3 months later. Participants A total of 108 community‐dwelling 65‐ to 90‐year‐old men. Measurements Testosterone and IGF‐1 levels, body composition (DEXA), 1‐repetition maximum (1‐RM) strength, stair‐climbing power, quality‐of‐life (QOL) and activity questionnaires, AEs. Results Despite improvements in body composition during treatment, residual benefits 3 months later (week 28) were variable. For participants with improvements exceeding their week‐17 median changes, benefits were sustained at week 28 for lean body mass (1·45 ± 1·63 kg, 45% of week‐17 values, P < 0·0001 vs baseline), appendicular skeletal muscle mass (ASMM, 0·71 ± 1·01 kg, 42%, P < 0·0001), total fat (?1·06 ± 2·18 kg, 40%, P < 0·0001) and trunk fat (?0·89 ± 1·42 kg, 50%, P < 0·0001); retention of ASMM was associated with greater week‐16 protein intake (P = 0·01). For 1‐RM strength, 39%–43% of week‐17 improvements (P ≤ 0·05) were retained and associated with better week‐17 strength (P < 0·0001), change in testosterone from week 17‐to 28 (P = 0·004) and baseline PASE (P = 0·04). Framingham 10‐year cardiovascular risks were low (～14%), did not worsen and improved by week 28 (P = 0·0002). The hypothalamic‐pituitary‐gonadal axis recovered completely. Conclusions Durable improvements in muscle mass, strength and fat mass were retained 3 months after discontinuing hormone supplementation in participants with greater than median body composition changes during treatment, but not in others with smaller gains. AEs largely resolved after intervention discontinuation. Additional strategies may be needed to sustain or augment muscle mass and strength gains achieved during short‐term hormone therapy.     

Cholecalciferol supplementation in chronic kidney disease: restoration of vitamin d status and impact on parathyroid hormone

Background/Aims: Hypovitaminosis D is highly prevalent among patients with chronic kidney disease (CKD) and has been associated with poor outcome. We aimed to test the effect of a protocol of cholecalciferol supplementation on the restoration of vitamin D status and on parathyroid hormone (PTH) levels in patients with CKD. Methods: This was a prospective interventional study of 6 months. Forty-five CKD patients (stages 3 and 4) with 25-hydroxyvitamin D deficiency [25(OH)D <15 ng/ml] were included. Patients received a weekly dose of 50,000 IU of cholecalciferol during 3 months, and 50,000 IU/month thereafter for those who had achieved 25(OH)D ≥30 ng/ml. Results: At 3 months, 78% of the patients restored their vitamin D status. At 6 months, only 43% of those patients maintained adequate vitamin D status. PTH decreased at 3 months (p = 0.02) but returned to baseline levels after 6 months. Fibroblast growth factor 23 increased at 3 months (p = 0.001) and returned to initial levels at 6 months. No changes were found in serum 1,25(OH)(2)D, ionized calcium and phosphorus. Conclusions: A weekly dose of 50,000 IU of cholecalciferol for 3 months restored the vitamin D status of most patients and led to a reduction in PTH. The monthly dose of 50,000 IU appears not to be sufficient to maintain the levels of 25(OH)D.     

Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men

OBJECTIVES: To study the effects of vitamin D supplementation in healthier populations of men. DESIGN: : Randomized, controlled trial. SETTING: General clinical research center. PARTICIPANTS: Sixty-five healthy, community-dwelling men (mean age+/-standard deviation=76+/-4, range 65-87). INTERVENTION: Cholecalciferol (1,000 IU/d) or placebo supplementation for 6 months; all received 500 mg supplemental calcium. MEASUREMENTS: Upper and lower extremity muscle strength and power, physical performance and activity, health perception, calcium and vitamin D intake, and biochemical assessment, including 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and ionized calcium levels. RESULTS: The levels of 25OHD increased and PTH decreased in the cholecalciferol group, whereas there were no significant changes in the control group (P<.001). Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score. Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score. No significant difference in strength, power, physical performance, or health perception was found between groups. CONCLUSION: The 25OHD or PTH levels correlated with physical activity and physical performance in older, community-dwelling men with normal 25OHD status. Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy, older men. Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin D.     

The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism*

OBJECTIVE The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with blosynthetic human GH in hypopituitary adults on aspects of calcium homeostatis, bone metabolism and bone mineral mass. PATIENTS Forty hypopituitary adults (21 females and 19 males; aged 19–67 years). DESIGN A prospective randomized double-blind placebo-controlled trial lasting for 6 months. PROTOCOL Following baseline assessments, GH was given in a daily dose of 0·02–0·05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. MEASUREMENTS Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. RESULTS Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I Increased significantly on GH treatment (mean ± SD) (GH: 276 ± 197 vs P: 88 ± 50 μg/l, P < 0 0001 at 6 months). Plasma calcium increased slightly but significantly in the GH-treated group (2·23 ± 0·11–2·29 ± 0·11 mmol/l, P<0·05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2·29 ± 0·11; P, 2·26 ± 0·09 mmol/l). Plasma phosphate increased on GH (GH: 1·02±0·23–1·32±0·19; P: 0·99±0·16–0·96±0·12 mmol/l over the 6 months of treatment, P<0·001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104±32 vs P: 69±32 U/I, P<0·01, osteocalcin: GH: 17·2±8·0 vs P: 5·3±3·2 μg/l, P<0·001 and P1CP: GH: 207 ± 152 vs P: 93±31 μg/l, P<0·01). There was no difference in the intact parathyroid hormone level (GH: 31 ± 14 vs P:31 ± 15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. CONCLUSION In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.     

Association between plasma 25-OH vitamin D and testosterone levels in men

Objective  A small randomized controlled trial suggested that vitamin D might increase the production of testosterone in men, which is supported by experimental studies in animals and a cross‐sectional study showing positive associations between plasma 25‐hydroxyvitamin D [25(OH)D] and testosterone and concordant seasonal variation of both biomarkers. Design and Measurements  We investigated the cross‐sectional association of plasma 25(OH)D levels and total and free testosterone measured by immunoassay in 1362 male participants of the Health Professionals Follow‐up Study who were selected for a nested case–control study on prostate cancer using multivariate‐adjusted linear and restricted cubic spline regression models. Results  25(OH)D was positively associated with total and free testosterone levels. From the lowest to the highest 25(OH)D quintile, multivariate‐adjusted means (95% confidence interval) were 18·5 (17·7; 19·4), 19·4 (18·6; 20·2), 19·6 (18·8; 20·4), 20·1 (19·3; 20·9) and 20·0 (19·1; 20·8; P‐trend = 0·003) for total testosterone and 97·7 (93·9; 101·5), 98·2 (94·1; 102·2), 99·2 (95·2; 103·2), 100·7 (96·9; 104·5) and 101·5 (97·6; 105·4; P‐trend = 0·03) for free testosterone. The shapes of the dose–response curves indicate that the association between 25(OH)D and total and free testosterone is linear at lower levels of 25(OH)D (below approximately 75–85 nmol/l), reaching a plateau at higher levels. Unlike for 25(OH)D, we did not observe any seasonal variation of testosterone concentrations. Conclusion  This study supports previously reported positive associations between vitamin D and testosterone although we did not observe parallel seasonal variation patterns. Possible causality and direction of the vitamin D–testosterone association deserve further scientific investigation.     

Vitamin D deficiency and aging: implications for general health and osteoporosis

Vitamin D deficiency is extremely prevalent in the elderly. Most often the first symptoms are caused by myopathy with muscle pain, fatigue, muscular weakness and gait disturbances. More severe deficiency causes osteomalacia with deep bone pain, reduced mineralization of bone matrix and low energy fractures. Recent data also suggest that hypovitaminosis D increases the risk of cancer of the prostate, colon and breast. Thus, hypovitaminosis D is associated with many diseases associated with aging. In order to diagnose hypovitaminosis D, the assessment of serum levels of 25-hydroxy vitamin D is mandatory. Screening based on other markers like alkaline phosphatase and parathyroid hormone (PTH) will be incomplete. The treatment of hypovitaminosis D is simple with administration of combined calcium (1 g) and vitamin D supplements(calciferol, at least 800 IU). Severe cases may demand initial parenteral administration of vitamin D (repeated injections of 300,000 IU 2–3 times with monthly intervals). More potent analogues are rarely needed. One should aim at achieving S-25(OH)D values in the range 50–100 nmol/l. This revised version was published online in July 2006 with corrections to the Cover Date.     

Adrenocorticotrophic hormone (ACTH) responsiveness to ghrelin increases after 6 months of ketoconazole use in patients with Cushing's disease: comparison with GH-releasing peptide-6 (GHRP-6)

Background In Cushing’s disease (CD), adrenocorticotrophic hormone (ACTH)/cortisol responses to growth hormone secretagogues (GHS), such as ghrelin and GHRP‐6, are exaggerated. The effect of clinical treatment of hypercortisolism with ketoconazole on ACTH secretion in CD is controversial. There are no studies evaluating ACTH/cortisol responses to GHS after prolonged ketoconazole use in these patients. Objective To compare ghrelin‐ and GHRP‐6‐induced ACTH/cortisol release before and after ketoconazole treatment in patients with CD. Design/patients Eight untreated patients with CD (BMI: 28·5 ± 0·8 kg/m²) were evaluated before and after 3 and 6 months of ketoconazole treatment and compared with 11 controls (BMI: 25·0 ± 0·8). Results After ketoconazole use, mean urinary free cortisol values decreased significantly (before: 613·6 ± 95·2 nmol/24 h; 3rd month: 170·0 ± 27·9; 6th month: 107·9 ± 30·1). The same was observed with basal serum cortisol (before: 612·5 ± 69·0 nmol/l; 3rd month: 463·5 ± 44·1; 6th month: 402·8 ± 44·1) and ghrelin‐ and GHRP‐6‐stimulated peak cortisol levels (before: 1183·6 ± 137·9 and 1045·7 ± 132·4; 3rd month: 637·3 ± 69·0 and 767·0 ± 91·0; 6th month: 689·8 ± 74·5 and 571·1 ± 71·7 respectively). An increase in basal ACTH (before: 11·2 ± 1·6 pmol/l; 6th month: 19·4 ± 2·7) and in ghrelin‐stimulated peak ACTH values occurred after 6 months (before: 59·8 ± 15·4; 6th month: 112·0 ± 11·2). GHRP‐6‐induced ACTH release also increased (before: 60·7 ± 17·2; 6th month: 78·5 ± 12·1), although not significantly. Conclusions The rise in basal ACTH levels during ketoconazole treatment in CD could be because of the activation of normal corticotrophs, which were earlier suppressed by hypercortisolism. The enhanced ACTH responses to ghrelin after ketoconazole in CD could also be due to activation of the hypothalamic–pituitary–adrenal axis and/or to an increase in GHS‐receptors expression in the corticotroph adenoma, consequent to reductions in circulating glucocorticoids.     

Impact of vitamin D supplementation on adiposity in African-Americans

Background:

African-Americans have higher rates of obesity-associated chronic diseases. Serum 25-hydroxyvitamin D (25(OH)D) shows an inverse association with obesity status. We investigated whether vitamin D supplementation changes body mass index (BMI).

Subjects:

In total, 328 overweight African-Americans were enrolled over three consecutive winter periods (2007–2010) into a randomized, double-blind, placebo-controlled trial to receive cholecalciferol supplementation (0, 1000 international units (IU), 2000 IU or 4000 IU per day) for 3 months. Plasma concentrations of 25(OH)D and anthropometric measurements were done at baseline, 3 and 6 months.

Results:

At 3 months, vitamin D supplementation in three dose groups (1000 IU, 2000 IU or 4000 IU per day) did not cause any significant changes in BMI as compared with placebo group 3-month change in BMI per 1000 IU per day estimate (SE): 0.01 (0.039); P=0.78.

Conclusions:

In overweight African-Americans, short-term high-dose vitamin D supplementation did not alter BMI.     

Vitamin D deficiency and treatment in Iraqi patients with primary fibromyalgia syndrome

Aim of the workTo establish the frequency of vitamin D deficiency in patients with primary fibromyalgia syndrome (FMS) in Basrah, Iraq, and to evaluate the effectiveness of vitamin D supplements in managing disease symptoms.Patients and methods160 FMS patients and 160 matched healthy controls were studied. Serum vitamin D levels were measured. Patients were randomly assigned to one of three treatment groups: Group 1 receiving antidepressant (amitriptyline 10 mg/day); group 2 treated with vitamin D (cholecalciferol 50,000 IU/week) and group 3 received both. All treatments were followed-up for 3 months.ResultsThe frequency of vitamin D deficiency was high (95%). The mean age of patients was 34.3 ± 9.5 years and 92.5% were females. The widespread pain index (WPI) scores significantly improved after 12 weeks in groups 2 and 1 (5.3 ± 3.4 and 7.9 ± 3.4 respectively) compared to baseline (11.9 ± 2.8 and 13.4 ± 2.6 respectively; p = 0.003). The WPI scores of the patients in group 3 improved early into week 4 (3.3 ± 2.7) and continued to improve at weeks 8 and 12 (2.7 ± 2.6 and 1.96 ± 1.6). There were clinically significant improvement in the patients in all treatment groups, most notably in the symptoms severity score (SSS) of fatigue, waking unrefreshed and cognitive impairment. Effects were greatest in the group treated with vitamin D and antidepressants.ConclusionVitamin D deficiency is common in FMS patients and it is associated with worsening of symptoms. Vitamin D supplementation in deficient FMS patients is associated with significant improvement. Screening of FMS patients for hypovitaminosis D is recommended.     

Vitamin D insufficiency prior to bariatric surgery: risk factors and a pilot treatment study

Objective To assess vitamin D status and the influences of race, sun exposure and dietary vitamin D intake on vitamin D levels, and to evaluate two vitamin D repletion regimens in extremely obese patients awaiting bariatric surgery. Methods A cross‐sectional analysis of dietary vitamin D, sun exposure, PTH [intact (iPTH) and PTH(1‐84)] and 25‐hydroxyvitamin D (25OHD; differentiated 25OHD2 and 25OHD3) in 56 obese [body mass index (BMI) > 35 kg/m²] men and women (age 20–64 years). In a pilot clinical trial, 27 subjects with 25OHD levels < 62 nmol/l were randomized to receive ergocalciferol or cholecalciferol for 8 weeks. Results Serum 25OHD was low (mean 45 ± 22 nmol/l) and was inversely associated with BMI (r = ?0·36, P < 0·01). Each BMI increase of 1 kg/m² was associated with a 1·3 nmol/l decrease in 25OHD (P < 0·01). BMI, sun exposure, African American race and PTH predicted 40% of the variance in 25OHD (P < 0·0001). Serum 25OHD significantly increased at 4 and 8 weeks in both treatment groups (P < 0·001), whereas PTH(1‐84) declined significantly in subjects treated with cholecalciferol (P < 0·007) and tended to decrease following ergocalciferol (P < 0·09). Conclusions In severely obese individuals, those who are African American, have higher BMI and limited sunlight exposure are at greatest risk for vitamin D insufficiency. These demographic factors can help to identify at‐risk patients who require vitamin D repletion prior to bariatric surgery. Commonly prescribed doses of ergocalciferol and cholecalciferol are effective in raising 25OHD. Further investigation is needed to evaluate whether these regimens have differential effects on PTH, and to determine the optimal regimen for vitamin D repletion in the extremely obese patient.