Threshold value of serum 25-hydroxyvitamin D concentration in relation to elevated serum parathyroid hormone concentrations in elderly Japanese women

This study was designed to determine the threshold value for 25-hydroxyvitamin D [25(OH)D] concentration in relation to elevated serum parathyroid hormone (PTH) concentrations in elderly Japanese women. The subjects were 582 noninstitutionalized, ambulant women who lived in a community in Japan. Serum 25(OH)D concentrations were determined using the Nichols Advantage chemiluminescent assay, and serum intact PTH concentrations were determined with a two-site immunoradiometric assay. Demographic characteristics, calcium intake, and serum 1,25(OH)₂D levels were also determined. The average age, body mass index (BMI), and calcium intake of the subjects were 74.5 years (SD 4.5), 23.3 kg/m² (SD 3.4), and 579 mg/day (SD 248), respectively. The serum log-transformed intact PTH concentration was significantly predicted by the serum 25(OH)D concentration (r = −0.147, P = 0.0004), but not by age, BMI, the serum log-transformed 1,25(OH)₂D concentration, or the log-transformed calcium intake. Analysis of variance with Dunnett's multiple comparisons showed that mean serum intact PTH concentrations with serum 25(OH)D concentrations less than 30 nmol/l (mean intact PTH = 5.89 pmol/l, P < 0.0001) and in the range 30–39 nmol/l (mean intact PTH = 4.54 pmol/l, P = 0.0067) were significantly higher than mean intact PTH concentrations for serum 25(OH)D concentrations greater than 50 nmol/l (mean intact PTH = 3.65 pmol/l, the baseline level), but the mean serum intact PTH concentration for 25(OH)D concentrations in the range 40–49 nmol/l (mean intact PTH = 3.70 pmol/l, P = 0.9975) was not. We conclude that serum 25(OH)D for ambulant elderly Japanese women should be maintained at 40 nmol/l or higher.     

Vitamin D deficiency in the elderly in Athens,Greece

Vitamin D deficiency characterized by low 25-hydroxyvitamin D [25(OH)D] levels has been found to be prevalent among the elderly in many regions of the world. To investigate the vitamin status in elderly community-living persons in Athens, we measured 25(OH)D and parathyroid hormone (PTH) in elderly persons and young blood donors during the winter and summer. The changes in these parameters in a subgroup of the elderly were studied longitudinally. The blood donors had mean 25(OH)D levels similar in winter and summer and twice as high in winter compared to the elderly. At the end of the winter, about 20% of the elderly had severe vitamin D deficiency, with 25(OH)D below 25 nmol/l, and only 6.5% could be judged as vitamin D sufficient with values above 80 nmol/l. The situation improved during summer, although 64.8% of the elderly continued to have levels below 80 nmol/l. Mean plasma PTH in the elderly in summer was not different from that of blood donors; however, it was doubled during the winter. Regression of PTH on 25(OH)D demonstrated that PTH starts to rise when 25(OH)D falls below approximately 80 nmol/l. We conclude that severe vitamin deficiency associated with secondary hyperparathyroidism is not uncommon in the elderly in Athens during the winter; it subsides during summer, although only one-third of the elderly population attain vitamin D sufficiency during summer. We found that a threshold value of 25(OH)D exists at approximately 80 nmol/l, below which secondary hyperparathyroidism ensues, as described previously.     

Age-related decrease in serum 25-hydroxyvitamin D concentrations in the frail elderly: a longitudinal study

Several cross-sectional studies have demonstrated an age-related decrease in serum 25-hydroxyvitamin D [25(OH)D] concentrations. No prospective studies, however, have been conducted to examine this correlation to date. The objectives of this study were to measure age-related changes in serum 25(OH)D concentrations and to identify predictors of change in serum 25(OH)D concentrations in the frail elderly during a 2-year follow-up period. Eighty elderly subjects (48 women and 32 men) were selected from people utilizing the long-term care insurance system in a community in Japan. All subjects participated in both the baseline and follow-up (2 years later) medical examinations. Baseline measurements included age, height, body mass index, and weight. Additionally, levels of activities of daily living (Barthel index), grip strength, lifestyle, serum 25(OH)D, intact parathyroid hormone (PTH), albumin, total protein, and creatinine concentrations were also determined at baseline. The average age of the subjects was 82.1 years (SD, 8.8). The 2-year decrease in serum 25(OH)D concentrations was calculated to be 6 nmol/l. Multiple linear regression analyses found that the 2-year change (Δ) in the log-transformed 25(OH)D was associated with Δalbumin (β = 0.503, R ² = 0.288, P < 0.0001), and Δlog-transformed intact PTH was associated with baseline creatinine (β = 0.453, R ² = 0.142, P = 0.0006) and Δlog-transformed 25(OH)D (β = −0.512, R ² = 0.103, P = 0.0037). In conclusion, serum 25(OH)D concentrations decreased in the 2-year follow-up. This information is useful for the maintenance of vitamin D status and prevention of vitamin D insufficiency in the frail elderly.     

Vitamin D Status During Puberty in French Healthy Male Adolescents

The vitamin D status was determined on one to four occasions either after summer (September–October) or after winter (March–April) in 175 male adolescents (13–17 years), resulting in 394 measurements of serum 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH). The subjects lived in a rural area to the north of Paris (49° N). After summer the 25(OH)D concentration was 58.5 ± 18.0 nmol/l (mean ± SD), while after winter it had fallen to 20.6 ±6.0 nmol/l (p= 0.0001). Meanwhile the iPTH concentration was 2.76 ± 0.97 pmol/l (mean ± SD) after summer and increased to 4.20 ± 1.21 pmol/l after winter (p= 0.0001). All the results were pooled and a nonlinear population model with random parameters was used to describe the relationship between serum iPTH and 25(OH)D. When the concentration of 25(OH)D was higher than 83 nmol/l, an iPTH mean ‘plateau’ level at 2.48 pmol/l was reached. When 25(OH)D concentrations fell below 83 nmol/l, the increase in iPTH concentration accelerates, and when the mean 25(OH)D concentration was equal to or lower than 10 nmol/l the mean iPTH level (4.97 pmol/l) was twice as high as the ‘plateau’ value. Received: 26 November 1998 / Accepted: 15 February 1999     

Low levels of 25-hydroxy vitamin D are associated with elevated parathyroid hormone in healthy adolescent females

This study aimed to investigate the relationship between 25-hydroxyvitamin D [25(OH)D)] and parathyroid hormone (PTH) levels in adolescent females residing in a northern climate. Concern regarding vitamin D status in this population is due to limited sunlight exposure in northern latitudes, decreased outdoor recreational activities, as well as decreased conversion in black girls from increased skin pigmentation. In this cross-sectional analysis, serum samples were assayed for 25(OH)D using competitive protein binding (CPB) assay and PTH with immuno-radiometric (RIA) procedures. Four hundred postmenarcheal females (12–18 years) residing in northeastern Ohio were recruited. Subjects were excluded if they had a history of bone, kidney, or liver disease, or used medications that affect bone. The primary goal was to determine serum 25(OH)D concentrations in relation to circulating PTH levels in a population of adolescent girls. The Spearman correlation test was used to compare PTH and 25(OH)D. Fit multiple split models were run to determine change in slope of the regression line when 25(OH)D and PTH were plotted. Analysis of variance was determined using modeled means with differences by race and season in the final model. Unadjusted mean serum 25(OH)D and PTH levels were 55.0±30.4 nmol/l and 39.4±20.6 ng/l, respectively. Blacks had lower 25(OH)D and higher PTH compared with non-blacks (P<0.0001), especially during the winter months. Decreasing 25(OH)D was inversely correlated with PTH (r=–0.314) (P<0.0001), and at concentrations of 25(OH)D 90 nmol/l, an increase in PTH was observed. Adolescents are at risk for decreased serum 25(OH)D concentrations, especially black girls. We found that the widely used cutoff for vitamin D deficiency is associated with increasing PTH levels and is below the inflection point for a change in the slope of the regression line. Our results support the need for further research to establish optimal vitamin D status in adolescent girls.     

Impact of calcium and vitamin D insufficiencies on serum parathyroid hormone and bone mineral density: Analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV‐3, 2009 and KNHANES V‐1, 2010)

The relative contributions of calcium and vitamin D to calcium metabolism and bone mineral density (BMD) have been examined previously, but not in a population with very low calcium intake. To determine the relative importance of dietary calcium intake and serum 25‐hydroxyvitamin D [25(OH)D] concentration to calcium metabolism and bone mass in a population with low calcium intake, a total of 4662 adults (2567 men and 2095 women) ≥50 years of age from the 2009–2010 Korea National Health and Nutrition Examination Survey (KNHANES) were divided into groups according to dietary calcium intakes (quintiles means: 154, 278, 400, 557, and 951 mg/d) and serum 25(OH)D concentrations (<50, 50–75, and >75 nmol/L). Serum intact parathyroid hormone (PTH) and femoral neck and lumbar spine BMD were evaluated according to dietary calcium intake and serum 25(OH)D. Mean calcium intake was 485 mg/d; mean serum 25(OH)D concentration was 48.1 nmol/L; PTH was 68.4 pg/mL; femoral neck BMD was 0.692 g/cm²; and lumbar spine BMD was 0.881 g/cm². Lower dietary calcium intakes were significantly associated with higher serum PTH concentrations and lower femoral neck BMD, not only at lower (<50 nmol/L) but also at higher (>75 nmol/L) serum 25(OH)D concentrations. Serum PTH was highest and femoral neck BMD was lowest in the group, with a serum 25(OH)D less than 50 nmol/L. In this low‐intake population, calcium intake is a significant determinant of serum PTH and BMD at higher as well as lower 25(OH)D levels. This finding indicates that low calcium intake cannot be compensated for with higher 25(OH)D levels alone. As expected, serum 25(OH)D levels were inversely associated with serum PTH and BMD. A calcium intake of at least 668 mg/d and a serum 25(OH)D level of at least 50 nmol/L may be needed to maintain bone mass in this calcium deficient population. © 2013 American Society for Bone and Mineral Research.     

Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents

Summary The effect of equivalent oral doses of vitamin D3 600 IU/day, 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a randomized clinical trial in nursing home residents. A daily dose was more effective than a weekly dose, and a monthly dose was the least effective. Introduction It is assumed that equivalent daily, weekly or monthly doses of vitamin D3 equally influence vitamin D status. This was investigated in a randomized clinical trial in nursing home residents. Methods The study was performed in ten nursing homes including 338 subjects (76 male and 262 female), with a mean age of 84 (± SD 6.3 years). They received oral vitamin D3 either 600 IU/day, or 4200 IU/week, or 18,000 IU/month or placebo. After 4 months, calcium was added during 2 weeks, 320 mg/day or 640 mg/day or placebo. Outcome: serum levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone turnover markers. Statistical approach: linear multilevel analysis. Results At baseline, mean serum 25(OH)D was 25.0 nmol/L (SD 10.9), and in 98%, it was lower than 50 nmol/L. After 4 months, mean serum 25(OH)D levels increased to 62.5 nmol/L (after daily vitamin D3 69.9 nmol/L, weekly 67.2 nmol/L and monthly 53.1 nmol/L, P < 0.001 between groups). Median serum PTH levels decreased by 23% (p < 0.001). Bone turnover markers did not decrease. Calcium supplementation had no effect on serum PTH and bone turnover. Conclusion Daily vitamin D was more effective than weekly, and monthly administration was the least effective.     

Wintertime Vitamin D Deficiency in Male Adolescents: Effect on Parathyroid Function and Response to Vitamin D3 Supplements

The first part of this study consisted of an 18 month follow-up of the vitamin D status and parathyroid function in a group of 54 French male adolescents, aged from 13 to 16 years old and all pupils of a jockey training school. During the 18 month period four samplings were made, one every 6 months. The first was during September of the first year, the second and third during March and October of the second year, and the last in March of the third year. Therefore we had two main periods: summer and winter. The summer 25-hydroxyvitamin D (25(OH)D) concentrations were higher (71.6 ± 19.9 and 52.4 ± 16.5 nmol/l) than the winter ones (20.4 ± 6.9 and 21.4 ± 6.1 nmol/l). Conversely, the winter intact parathyroid hormone (iPTH) serum levels (4.18 ± 1.18 and 4.11 ± 1.35 pmol/l) were higher than the summer ones (2.44 ± 0.82 and 2.71 ± 0.71 pmol/l). At the two winter time points the 25(OH)D concentrations were lower than 25 nmol/l (10 ng/ml) in 72% (2nd year) and 68% (3rd year) of the adolescents. In the second part of the study we tried a vitamin D₃ supplementation procedure designed to maintain the 25(OH)D and iPTH postsummer serum levels throughout the winter. Pairs of male adolescents matched for height, weight and Tanner pubertal stage were randomly assigned to either vitamin D₃ supplementation (2.5 mg, i.e., 100 000 IU) administered orally at three specific periods (end of September, November and January) or no vitamin D₃ treatment (control subjects). Blood was collected just before the first intake of vitamin D₃ and 2 months after the last intake (March). The control subjects had blood drawn at the same time points. In the vitamin D₃-treated subjects, the concentrations of 25 (OH)D (55.3 ± 11.5 nmol/l) and of iPTH (3.09 ± 1.16 pmol/l) in March and September (53.8 ± 12.3 nmol/l and 2.75 ± 1.26 pmol/l) were not significantly different. In the control subjects, March 25(OH)D levels (21.0 ± nmol/l were low, with values below 25 nmol/l in 78% of subjects, and iPTH concentrations (3.97 ± 1.08 pmol/l) were significantly (p<0.001) higher than in September (2.91 ± 0.81 pmol/l). The constant vitamin D wintertime deficiency and wintertime rise in iPTH in adolescent French males throughout puberty has been demonstrated. In adolescents with low dairy calcium intakes, the vitamin D₃ treatment was sufficient to maintain 25(OH)D concentrations at their summer levels throughout winter and to prevent an excessive wintertime rise in iPTH levels. Received: 6 February 2001 / Accepted: 9 May 2001     

Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia

Purpose Vitamin D deficiency leads to secondary hyperparathyroidism and osteomalacia, and both conditions are associated with fractures, the most severe being hip fracture. The serum 25-hydroxyvitamin D level depends on latitude and season. Yekaterinburg is situated at a high latitude and the duration of winter is about 5 months. Methods In this study, the serum 25(OH)D and PTH concentrations, and the prevalence of hypovitaminosis D in elderly people, inhabitants of Yekaterinburg, were investigated. The study was performed on 63 people with hip fracture (mean age, 68.8 years) and 97 independently living elderly people (mean age, 70.2 years). Results Serum 25(OH)D (mean±SD) in the hip fracture group was 22.4±11.4 nmol/L, significantly lower than in control group, which was 28.1±10.1 nmol/L. The percentage of patients with severe hypovitaminosis D (<25 nmol/L) in the hip fracture group was 65%, compared to 47% in the control group (p<0.05). The prevalence of hypovitaminosis D among hip fracture patients, as well as among independently living elderly people in Yekaterinburg, was high. Conclusion Supplementation of vitamin D in elderly people with and without fracture might prevent secondary hyperparathyroidism, osteomalacia and fractures.     

Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis

Summary  We performed a meta-analysis of cross-sectional studies on serum 25(OH)D status globally. Serum 25(OH)D levels on average were 54 nmol/l, were higher in women than men, and higher in Caucasians than in non-Caucasians. There was no trend in serum 25(OH)D level with latitude. Vitamin D deficiency was widespread. Introduction  We studied vitamin D status (expressed as serum 25-hydroxy-vitamin D [25(OH)D]) in native subjects worldwide. Methods  Meta-analysis and meta-regression of studies reporting on 25(OH)D in healthy subjects retrieved from Pubmed, Embase and Web of Science using the terms “serum”, “25-hydroxy-vitamin D”, “cholecalciferol”, and “human”. A total of 394 studies were included. Results  The mean 25(OH)D level was 54 nmol/l (95% CI: 52–57 nmol/l). Women had borderline significantly higher 25(OH)D levels than men, and Caucasians had higher levels than non-Caucasians. 25(OH)D levels were higher in subjects aged >15 years than in younger subjects. Unadjusted there was no significant decrease in 25(OH)D with latitude (slope of curve −0.03 ± 0.12 nmol/l per degree latitude north or south of equator, p = 0.8). There was a significant decline with latitude for Caucasians (−0.69 ± 0.30 nmol/l per degree, p = 0.02), but not for non-Caucasians (0.03 ± 0.39 nmol/l per degree, p = 0.14). After adjustment for age, gender, and ethnicity, no overall correlation was present between 25(OH)D and latitude (−0.29 ± 0.24 nmol/l per degree, p = 0.23). Conclusion  There was no overall influence of latitude on 25(OH)D. However, in separate analyses 25(OH)D decreased with latitude in Caucasians but not in non-Caucasians. A widespread global vitamin D insufficiency was present compared with proposed threshold levels. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland

Vitamin D deficiency may be one important contributing risk factor for an osteoporotic fracture among elderly. We analyzed serum 25-hydroxyvitamin D [S-25(OH)D] status in patients with an acute hip fracture in southeastern Finland (61°N). Consecutive patients with a fresh hip fracture ( n =223) in two Finnish hospitals during 12 months and 15 months were registered prospectively. S-25(OH)D concentrations (nmol/l) were measured by radioimmunoassay-method. Hypovitaminosis D was defined as S-25(OH)D <37.5 nmol/l and severe hypovitaminosis D:<20 nmol/l. The highest threshold of S-25(OH)D in our analysis was >74 nmol/l. The seasonal variation in S-25(OH)D concentrations was followed. Hypovitaminosis D was found in 53% of the patients. In 9% hypovitaminosis D was severe. Half (50%) of the patients living in their own homes, 55% of those in residential homes, and 61% of institutionalized elderly had hypovitaminosis D. Patients who used both vitamin D and calcium supplement had S-25(OH)D levels between 37.5 nmol/l and 74 nmol/l and >74 nmol/l more often than non-users ( Wx =3.85, p =0.0001). Most (41/61) of the patients who sustained the fracture during the late summer months had S-25(OH)D concentration 37.5 nmol/l, whereas, in winter months the situation was quite the opposite (24/67) ( Wx =3.42, p =0.0006). Twenty-two percent (50/223) had S-25(OH)D concentration >50 nmol/l and four patients >78 nmol/l. Half of the patients with a hip fracture suffered from hypovitaminosis D. The situation was worst in institutional and residential care, although there are personnel for taking care of vitamin D supplementation. In the late summer, one-third and in late winter two-thirds of the patients suffered from hypovitaminosis D. The geographical location of Finland indicates extensive efforts to increase the use of vitamin D supplements among elderly.     

Prevalence of Vitamin D Insufficiency in an Adult Normal Population

The vitamin D status of a general adult urban population was estimated between November and April in 1569 subjects selected from 20 French cities grouped in nine geographical regions (between latitude 43° and 51° N). Major differences in 25-hydroxyvitamin D (25(OH)D) concentration were found between regions, the lowest values being seen in the North and the greatest in the South, with a significant ‘sun’ effect (r = 0.72; p = 0.03) and latitude effect (r = -0.79; p = 0.01). In this healthy adult population, 14% of subjects exhibited 25(OH)D values ≤ 30 nmol/l (12 ng/ml), which represents the lower limit (< 2 SD) for a normal adult population measured in winter with the same method (RIA Incstar). A significant negative correlation was found between serum intact parathyroid hormone (iPTH) and serum 25(OH)D values (p < 0.01). Serum iPTH held a stable plateau level at 36 pg/ml as long as serum 25(OH)D values were higher than 78 nmol/l (31 ng/ml), but increased when the serum 25(OH)D value fell below this. When the 25(OH)D concentration became equal to or lower than 11.3 nmol/l (4.6 ng/ml), the PTH values reached the upper limit of normal values (55 pg/ml) found in vitamin D replete subjects. These results showed that in French normal adults living in an urban environment with a lack of direct exposure to sunshine, diet failed to provide an adequate amount of vitamin D. It is important to pay attention to this rather high prevalence of vitamin D insufficiency in the general adult population and to discuss the clinical utility of winter supplementation with low doses of vitamin D.     

High-dose oral vitamin D3 supplementation in the elderly

Summary  Daily dosing with vitamin D often fails to achieve optimal outcomes, and it is uncertain what the target level of 25-hydroxyvitamin D should be. This study found that large loading doses of vitamin D₃ rapidly and safely normalize 25OHD levels, and that monthly dosing is similarly effective after 3–5 months. With baseline 25OHD > 50 nmol/L, vitamin D supplementation does not reduce PTH levels. Introduction  There is concern that vitamin D supplementation doses are frequently inadequate, and that compliance with daily medication is likely to be suboptimal. Methods  This randomized double-blind trial compares responses to three high-dose vitamin D₃ regimens and estimates optimal 25-hydroxyvitamin D (25OHD) levels, from changes in parathyroid hormone (PTH), and procollagen type I amino-terminal propeptide (P1NP) in relation to baseline 25OHD. Sixty-three elderly participants were randomized to three regimens of vitamin D supplementation: a 500,000-IU loading dose; the loading dose plus 50,000 IU/month; or 50,000 IU/month. Results  The Loading and Loading + Monthly groups showed increases in 25OHD of 58 ± 28 nmol/L from baseline to 1 month. Thereafter, levels gradually declined to plateaus of 69 ± 5 nmol/L and 91 ± 4 nmol/l, respectively. In the Monthly group, 25OHD reached a plateau of ~80 ± 20 nmol/L at 3–5 months. There were no changes in serum calcium concentrations. PTH and P1NP were only suppressed by vitamin D treatment in those with baseline 25OHD levels <50 and <30 nmol/L, respectively. Conclusions  Large loading doses of vitamin D₃ rapidly and safely normalize 25OHD levels in the frail elderly. Monthly dosing is similarly effective and safe, but takes 3–5 months for plateau 25OHD levels to be reached.     

Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels

Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels.     

Rapid correction of low vitamin D status in nursing home residents

Summary  This prospective study finds that ergocalciferol 50,000 IU three times weekly for four weeks effectively and safely corrects vitamin D inadequacy in nursing home residents. Introduction  Low vitamin D status is common among nursing home residents and contributes to bone loss, falls and fractures. The objective of this study was to evaluate the efficacy and safety of short course, high dose, oral vitamin D₂ (ergocalciferol) treatment. Methods  This prospective study included 63 nursing home residents. The 25 with low vitamin D status (serum 25(OH)D ≤ 25 ng/ml) received oral ergocalciferol 50,000 IU three times weekly for four weeks; the others received no change to their routine care. Serum total 25(OH)D, 25(OH)D₂, 25(OH)D₃, calcium, parathyroid hormone (PTH), bone turnover markers and neuro-cognitive assessments were obtained at baseline and four weeks. Results  Mean total 25(OH)D concentration increased (p < 0.0001) from 17.3 to 63.8 ng/ml in the treated group and remained unchanged in the comparison group. Serum 25(OH)D₃ remained stable in the comparison group, but declined (p < 0.0001) with D₂ treatment from 15.4 to 9.1 ng/ml. Serum PTH trended down in the treatment group (p = 0.06). No treatment-induced improvement in ambulation, cognition or behavior was observed. No hypercalcemia or other adverse effects were observed with ergocalciferol treatment. Conclusion  Four weeks of oral vitamin D₂ supplementation effectively and safely normalizes serum 25(OH)D in nursing home residents.     

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

Skeletal and hormonal responses to sunlight deprivation in Antarctic expeditioners

Summary  Serum 25(OH)D levels decline without sunlight exposure. We studied 120 expeditioners to Antarctica to determine the skeletal and hormonal responses to sunlight deprivation. With emerging vitamin D insufficiency, serum calcium decreased, PTH increased, and bone loss at the proximal femur was observed. Baseline serum 25(OH)D levels >100 nmol/L prevented vitamin D insufficiency. Introduction  Vitamin D stores deplete without adequate sunlight exposure unless supplementation is provided. We studied 120 healthy adults who spent a year in Antarctica as a model for sunlight deprivation to define the timing and magnitude of the skeletal and hormonal responses to emerging vitamin D insufficiency. Methods  Fasting blood samples were assessed at baseline, 6 and 12 months for serum 25-hydroxyvitamin D (25(OH)D), osteocalcin (OC), bone formation (P1NP) and resorption (CTx), PTH and calcium. Lumbar spine and proximal femur BMD was measured using DXA. Differences over time were determined using repeated measures ANOVA. Percent changes were expressed as (Δ value/(value A + value B)/2) × 100. Relationships between outcome measures were determined using Spearman’s correlations. Results  Vitamin D insufficiency (<50 nmol/L) was observed in 85% of expeditioners by 6 months when serum calcium decreased and PTH increased (p < 0.01). By 12 months, OC increased by 7.4 ± 3.0% (p < 0.05), and BMD decreased by 1.0 ± 2.0% at the total proximal femur (p < 0.05). For those with vitamin D sufficiency at baseline (>50 nmol/L), sunlight deprivation produced vitamin D insufficiency within 4 months unless baseline values were >100 nmol/L. Conclusion  Supplementation may be necessary for expeditioners with limited access to UV light.     

Longitudinal Evaluation of Vitamin D Status in Healthy Subjects from Southern Italy: Seasonal and Gender Differences

Vitamin D status is currently considered among the relevant determinants of skeletal integrity. Since vitamin D levels present seasonal variations, we longitudinally studied young healthy men and women in order to investigate the related physiologic modifications of both calcium homeostasis and bone remodeling. Thirty-two men (mean age 39.4 ± 7.8 years) and 58 premenopausal women (aged 36.9 ± 6.4 years) from southern Italy were studied. In all subjects the following parameters were measured both in winter and in summer: serum calcium, phosphorus, creatinine, total alkaline phosphatase activity, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin (BGP), together with urinary calcium (Ca/Cr), total pyridinoline (Pyr/Cr) and deoxypyridinoline (d-Pyr/Cr), corrected for creatinine excretion. In both sexes 25OHD levels were significantly higher in summer, while PTH values were lower, than in winter. The prevalence of hypovitaminosis D, defined by concentrations of 25OHD lower than 30 nmol/l, was 17.8% in winter and 2.2% in summer in the whole sample, while it was 27.8% and 3.4%, respectively, among female subjects. Indeed male subjects did not display hypovitaminosis D, having throughout the year significantly higher calcium and 25OHD levels together with lower PTH values, than the women. Moreover, alkaline phosphatase total activity was more elevated in men both in winter and in summer. In women, during winter, bone remodeling markers levels were higher while urinary calcium levels were lower than in summer. In the whole sample serum 25OHD correlated positively with serum calcium and inversely with PTH. The seasonal percentage variations in PTH were inversely correlated with those of Ca/Cr. Our results show a relatively high prevalence of subclinical vitamin D deficiency among young healthy women from southern Italy. Significant gender-specific differences have been demonstrated in both calcium homeostasis and skeletal remodeling indexes; the seasonal fluctuations in the vitamin D–PTH axis are accompanied by cyclical variations of bone turnover rate, which were more pronounced in women. Received: 11 January 2001 / Accepted: 6 July 2001     

Adverse interaction of low‐calcium diet and low 25(OH)D levels on lumbar spine mineralization in late‐pubertal girls

No consensus has been reached on the serum 25‐hydroxyvitamin D [25(OH)D] levels required to ensure optimal bone health around menarche. We searched for a possible interaction of 25(OH)D levels and calcium intake on lumbar spine mineralization and on biologic features of bone metabolism in healthy late‐pubertal girls. Lumbar spine parameters (ie, area, mineral content, and density) and calcium intake were evaluated in 211 healthy white adolescent girls at pubertal stages IV–V (11 to 16.9 years), together with biologic markers of calcium and bone metabolism and with International External Quality Assessment Scheme for Vitamin D Metabolite (DEQAS)–validated serum 25(OH)D levels. A high prevalence of 25(OH)D levels ≤ 30 nmol/L (41%), ≤40 nmol/L (61%), and ≤50 nmol/L (70%) was found during winter–spring. Parathyroid hormone (PTH) levels were inversely associated with 25(OH)D levels (p = .0021). In contrast, lumbar spine mineral content and density were not associated with 25(OH)D, excepted when calcium intake was below 600 mg/day (p = .0081). Girls with such low calcium intake and 25(OH)D levels of 40 nmol/L or less (9% of the cohort) had a 0.4 to 0.7 SD lower mean areal bone mineral density Z‐score than girls with higher calcium intake and/or higher 25(OH)D status. The adverse association between lumbar spine mineralization and combined calcium deficiency–low 25(OH)D levels remained significant in the 91 girls who could be followed over 4 years after their initial evaluation. We conclude that low 25(OH)D levels (≤40 nmol/L) are observed frequently during winter–spring in late‐pubertal European girls, which may exacerbate the negative impact of calcium deficiency on lumbar spine mineralization. © 2010 American Society for Bone and Mineral Research.     

Serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in men: the Rancho Bernardo study

Introduction This study examined the distribution and determinants of serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) and their associations with bone mineral density (BMD) at the hip and spine in 414 older men (mean age 74 years) living in southern California.Methods At a clinic visit (1997–2000), demographic and lifestyle information, fracture history, and medication use were recorded; venous blood for serum 25OHD and PTH was obtained; and BMD was measured at the hip and spine.Results Only one man had vitamin D deficiency (25OHD <20 nmol/l), but 15.5% of the men had high parathyroid levels (PTH ≥65 pg/ml). The mean 25OHD and PTH levels were 109.0 nmol/l and 50.3 pg/ml, respectively. Overall, 21.5% used calcium and 9.7% used vitamin D supplements. Serum 25OHD decreased with age and was lowest in the winter; levels were higher in supplement users (vitamin D and/or calcium; p<0.01). Serum PTH did not vary by age or season, and it was lower in supplement users (p<0.01). After excluding 12 men who were outliers for serum 25OHD and PTH, there was no significant correlation between serum 25OHD and PTH (r=−0.05, p=0.3). In multiple adjusted models, serum 25OHD was positively associated with BMD at the hip (p=0.01) and spine (p=0.001). Serum PTH was moderately and inversely associated with BMD at the hip (p=0.04) but not at the spine (p=0.77).Conclusion We conclude that serum 25OHD is associated with bone health in older, community-dwelling men.