How well are the optimal serum 25OHD concentrations reached in high-dose intermittent vitamin D therapy? a placebo-controlled study on comparison between 100 000 IU and 200 000 IU of oral D3 every 3 months in elderly women.

OBJECTIVE: Intermittent dosing may improve adherence to vitamin D therapy. Dosing regimen should maintain optimal serum 25-hydroxyvitamin D (25OHD) levels over all the year. We compared two dosing regimens, the primary outcome being the percentage of 25OHD measurements reaching the targets of 75 nmol/l or 50 nmol/l after baseline. DESIGN: Randomized, placebo-controlled parallel group comparison. PATIENTS: Sixty women aged 75·0 ± 2·9 years. INTERVENTIONS: 100 000 IU (group 1D) or 200 000 IU (2D) of vitamin D3 or placebo orally every 3 months plus calcium 1 g daily for 1 year. MEASUREMENTS: Serum 25OHD, 1,25-dihydroxyvitamin D, PTH, sclerostin, ionized calcium, urinary calcium, renal function, bone turnover markers. RESULTS: Serum 25OHD increased, but the difference between two doses was of borderline significance (P = 0·0554; area under curve analysis). Immediate postadministrative increases were higher in the 2D vs 1D group (P < 0·05) after 3 and 6 months' dosing. In the 1D and 2D groups, 51·2% and 57·7% of all on-treatment measurements reached the target of 75 nmol/l. PTH levels differed marginally (P = 0·0759) due to tendency to lowering immediately after vitamin D boluses. Urinary calcium differed between the groups (P = 0·0193) due to increases 1 week after vitamin D dosing. CONCLUSIONS: The doses of 100 000 or 200 000 IU of oral cholecalciferol every 3 months were not capable of stabilizing 25OHD levels over the target of 75 nmol/l over the year. To improve the efficacy of high-dose vitamin D therapy, the interval between boluses has to be shortened instead of increasing their size.

The same annual dose of 292000 IU of vitamin D (cholecalciferol) on either daily or four monthly basis for elderly women: 1-year comparative study of the effects on serum 25(OH)D concentrations and renal function.

OBJECTIVE: Daily dosing of vitamin D supplements may be difficult among older people. Infrequent administration of 'megadoses' controlled by health care personnel may overcome adherence problem. We compared the efficacy and safety of two oral dosages (800 IU daily or 97333 IU four monthly) of vitamin D(3) resulting in the equal annual dose of 292000 IU. DESIGN: Randomized, double-blind, double-dummy parallel group comparison. Patients Forty women aged 69.3-78.8 years. INTERVENTIONS: Vitamin D(3) 400 IU twice daily (D group) or vitamin D(3) oil 97333 IU every 4 months (4 M group) for 1 year. All received 1 g of calcium daily. MEASUREMENTS: Serum 25-hydroxyvitamin D(3) [25(OH)D(3)] in relation to the target levels of 50-75 nmol/l, PTH, serum type I procollagen aminoterminal propeptide (PINP), serum and urine calcium, renal function. RESULTS: A quantity of 25OHD(3) increased more in D group than in 4 M group (P < 0.0001). All participants in D group and 67% in 4 M group had 25(OH)D(3) above 50 nmol/l at 12 months; the target level of 75 nmol/l was reached by 47% and 28% respectively. PTH did not show any seasonal perturbation in either group. PINP declined and urinary calcium rose similarly in the study groups over time (P < 0.0001). Renal function did not worsen in either group. CONCLUSIONS: In terms of serum 25(OH)D(3) concentrations, 800 IU daily was more efficient than a 97333 IU every 4 months. However, to increase adherence, the latter is still worth developing. Both treatments increased urinary excretion of calcium, but did not worsen renal function.

Risk factors for clinical stress fractures in male military recruits: a prospective cohort study.

This prospective study was aimed at evaluating risk factors for symptomatic stress fractures among 179 Finnish male military recruits, aged 18 to 20 years. The subjects were studied in the very beginning of the military service of 6 to 12 months in summer. Bone mineral content (BMC) and density (BMD) were measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip and heel ultrasound investigation was performed. Blood was sampled for determination of serum total and free testosterone, total and free estradiol, sex hormone-binding globulin (SHBG), procollagen type I N propeptide, total and carboxylated osteocalcin, tartrate-resistant acid phosphatase 5b, 25-hydroxyvitamin D (25-OHD), and intact parathyroid hormone (iPTH), as well as for studying the XbaI and PvuII polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene. Urine was collected for the determination of N-terminal cross-linking telopeptide of type I collagen. Muscle strength was measured and Cooper's test was performed. Current exercise, smoking, calcium intake, and alcohol consumption were recorded using a questionnaire. During military service, 15 men experienced a stress fracture, diagnosed with X-ray in 14 and with nuclear magnetic resonance in one man. Those who experienced a fracture were taller than those who did not (P = 0.047). The result of Cooper's test was worse in the fracture group than in the non-fracture group (P = 0.026). Femoral neck and total hip BMC and BMD, adjusted for age, weight, height, exercise, smoking, and alcohol and calcium intake were lower (P = 0.021-0.041) for the fracture group. Stress fractures associated with higher iPTH levels (P = 0.022) but not with lower 25-OHD levels. Bone turnover markers as well as sex hormone and SHBG levels were similar for men with and without stress fracture. There was no difference in the genetic analyses between the groups. In conclusion, tall height, poor physical conditioning, low hip BMC and BMD, as well as high serum PTH level are risk factors for stress fractures in male Finnish military recruits. Given the poor vitamin D status of young Finnish men, intervention studies of vitamin D supplementation to lower serum PTH levels and to possibly reduce the incidence of stress fractures are warranted.

Vitamin D status as a determinant of peak bone mass in young Finnish men.

Severe vitamin D deficiency causes rickets, but scarce data are available about the extent to which vitamin D status determines the development of the peak bone mass in young adults. Our aim was to evaluate the prevalence of vitamin D deficiency [serum 25-hydroxyvitamin D (25-OHD) less than the lower limit of the reference range of 20-105 nmol/liter] and the relationship between vitamin D status and peak bone mass among young Finnish men. A cross-sectional study of determinants of peak bone mass with data on lifestyle factors collected retrospectively was performed in 220 young men, aged 18.3-20.6 yr. One hundred and seventy men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content, bone mineral density, and scan area were measured in lumbar spine and upper femur by dual energy x-ray absorptiometry. Serum 25-OHD concentrations were followed prospectively for 1 yr. In July 2000, only 0.9% of the men had vitamin D deficiency, but 6 months later, in the winter, the respective percentage was 38.9%. After adjusting for age, height, weight, exercise, smoking, calcium, and alcohol intake, there existed a positive correlation between serum 25-OHD and bone mineral content at lumbar spine (P = 0.057), femoral neck (P = 0.041), trochanter (P = 0.010), and total hip (P = 0.025). The correlation coefficients for the bone mineral densities at the four measurement sites were 0.035, 0.061, 0.056, and 0.068, respectively. No correlation was found to scan area. We conclude that vitamin D deficiency is very common in Finnish young men in the winter, and it may have detrimental effects on the acquisition of maximal peak bone mass. As in Finland vitamin D supplementation to infants is now stopped at the age of 3 yr, it can be asked whether at our latitude it should be continued from that age onward, not for the prevention of rickets, but as prophylaxis for osteoporosis.