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     

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     

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.     

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.     

Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men

We determined the quantitative relationships between graded oral dosing with vitamin D₃, 25(OH)D₃, and 1,25(OH)₂D₃ for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 + 4 years, with usual milk consumption of 40.47 l/day and mean serum 25(OH)D of 67 + 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D₃ (25, 250 or 1250 mg/day for 8 weeks), 25(OH)D₃ (10, 20 or 50 mg/day for 4 weeks) and 1,25(OH)₂D₃ (0.5, 1.0 or 1.0 mg/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum calcium, parathyroid hormone, vitamin D₃, 25(OH)D and 1,25(OH)₂D immediately before and after treatment. In the three groups treated with vitamin D₃, mean values for circulating vitamin D₃ increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D₃ increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)₂D levels. However, treatment with 1,25(OH)₂D₃ increased circulating 1,25(OH)₂D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D₃ at 10 mg/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D₃ at 20 mg/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)₂D₃ at 0.5 mg/day would raise serum 1,25(OH)₂D by 17 pmol/l. Received: 4 August 1997 / Accepted: 14 October 1997     

Serum 25-hydroxyvitamin D levels and activities of daily living in noninstitutionalized elderly Japanese requiring care

To date, no study has investigated the nutritional status of vitamin D in frail elderly people living at home. The purposes of this study were to assess serum 25-hydroxyvitamin D (25[OH]D) levels and associated factors in noninstitutionalized elderly people who had various levels of physical disability, and to propose an adequate vitamin D nutritional status for the elderly by interpreting the serum 25(OH)D levels in relation to serum parathyroid hormone (PTH) levels in this population. Health examinations were conducted in the winter and summer of 2003. The subjects were 143 elderly people in the winter, and 120 elderly people in the summer, who all used the long-term care insurance system at home. Serum 25(OH)D concentrations were determined with a chemiluminescence protein-binding assay, and serum intact PTH concentrations were determined with an immunoradiometric assay. The subjects' disease histories and lifestyle information were obtained through an interview. Activities of daily living (ADL) levels were evaluated using the Barthel index, and grip strength was measured with a digital hand dynamometer. Average serum 25(OH)D levels in the winter and summer were 54.2 nmol/l (SD 29.0) and 53.3 nmol/l (SD 32.3), respectively, and intact PTH concentrations in the winter and summer were 4.2 pmol/l (SD 1.8) and 4.3 pmol/l (SD 1.8), respectively. The proportion of people who had a low 25(OH)D (<30 nmol/l) and high intact PTH levels (>6.9 pmol/l) were 15%–20% and 8%, respectively. Significant predictors of low serum 25(OH)D concentrations were low ADL levels, female sex, and low fish consumption in both seasons. Serum 25(OH)D concentrations of less than 50 nmol/l were associated with elevated serum intact PTH concentrations. In conclusion, elderly people requiring care at home are at high risk of hypovitaminosis D, and their low serum 25(OH)D levels are mainly associated with low ADL levels. In addition, maintenance of serum 25(OH)D concentrations above 50 nmol/l may prevent hypovitaminosis D-induced hyperparathyroidism.     

Calcidiol and PTH Levels in Women Attending an Osteoporosis Program

We performed a retrospective study of 237 patients attending a specialty osteoporosis practice. Secondary causes for reduced bone mineral density (BMD) were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age was 56 ± 13.8 years (mean ± SD). BMD was measured by dual-energy X-ray absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour urinary calcium were measured, and serum and urine protein (SPEP and UPEP) electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in iPTH levels. Among the osteoporotic patients (T score <−2.5 SD), 17% had 25(OH)D levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (−2.5 < T < −1.0 SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score ≤−1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D levels were inversely related to high iPTH values (r = 0.30, P < 0.0001). Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65 pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in 4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of 25(OH)D levels is recommended in the evaluation of secondary causes for reduced BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25 ng/ml, the level required to prevent increments in iPTH levels. Received: 9 February 1998 / Accepted: 1 October 1998     

Effect of Supplementation with Vitamin D3 and Calcium on Quantitative Ultrasound of Bone in Elderly Institutionalized Women: A Longitudinal Study

Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62–98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D₃ combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 ± 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 ± 1.2 and 11.7 ± 1.2 mg/l; normal range 6.4–40.2 mg/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 ± 3.2 and 44.6 ± 3.5 ng/l; normal range 10–70 ng/l, normal mean 31.8 ± 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p50.01) and a decrease in PTH by 18% (p50.05) and of alkaline phosphatase by 15% (p50.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p50.01) and an increase in PTH by 51% (p50.01), while the serum calcium level decreased by only 2% (p5 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p50.05), and decreased by 2.3% in the controls (p50.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p50.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D₃ in a population of elderly institutionalized women. Received: 23 February 1998 / Accepted: 19 October 1998     

Lifestyle and Biologic Contributors to Proximal Femur Bone Mineral Density and Hip Axis Length in Two Distinct Ethnic Groups of Premenopausal Women

Although relatively little is known about osteoporotic risk factors in women from the Indian subcontinent, osteoporotic fractures usually occur 10–20 years earlier in Indian men and women compared with their western Caucasian counterparts. The primary purpose of this cross-sectional study was to determine the relative contributions of ethnicity, reproductive history, body size (height, weight) and composition, bone turnover, serum 25(OH)vitamin D₃ [25(OH)D₃], dietary intake (of calcium, fiber and alcohol) and energy expenditure to femoral bone mineral density (BMD) in Indian and Pakistani (Indian/Pakistani; n= 47) versus American (n= 47) Caucasians. We also contrasted femoral BMD and hip axis length in these two distinct groups of premenopausal females living in the USA. The Indian/Pakistani (0.875 ± 0.096) women had lower (p= 0.0014) femoral BMD (g/cm²) than their American (0.937 ± 0.088) counterparts, placing them at greater osteoporotic risk. However, the shorter (p= 0.0002) hip axis length (cm) of the Indian/Pakistani (10.54 ± 0.57) versus American (11.11 ± 0.78) Caucasians might attenuate hip fracture risk in the former group. Significant contributors to proximal femur BMD were maximum non-pregnant lifetime weight, age at menarche, ratio of ∑central-to-peripheral skinfold thicknesses, calcium intake from milk and usual alcohol intake. Although serum 25(OH)D₃ and urinary N-telopeptide concentrations did not contribute to femoral BMD in the regression models, the lower (p<0.0001) serum 25(OH)D₃ (33.1 ± 16.5 vs 64.0 ± 22.0 nmol/l) and higher (p= 0.0004) urinary N-telopeptide (45.9 ± 43.3 vs 18.9 ± 18.7 nmol BCE/mmol) values in Indian/Pakistani versus American Caucasians, respectively, coupled with their lower BMD, places the Indian/Pakistani women at greater osteoporotic risk. These results suggest that a clinical trial to increase BMD and reduce osteoporotic risk is warranted in this ethnic group of premenopausal women. Received: 29 April 1998 / Accepted: 12 August 1998     

High Prevalence of Hypovitaminosis D among Free-Living Postmenopausal Women Referred to an Osteoporosis Outpatient Clinic in Northern Italy for Initial Screening

To establish the prevalence of hypovitaminosis D among free-living postmenopausal women referred to an osteoporosis outpatient clinic in Northern Italy, we evaluated 25-hydroxyvitamin D (25(OH)D) levels in 570 postmenopausal women who had been consecutively referred to our clinic in the 12 months beginning October 1995. Parathyroid hormone (PTH), serum calcium (Ca), creatinine (Cr) and osteocalcin (OC), urinary calcium (Ca24h) and creatinine (Cr24h), and the bone mineral density of the lumbar spine (LBMD) and femur (FBMD) were also measured. 1,25-Dihydroxyvitamin D (1,25(OH)₂D) concentrations were measured in 23 women. All women had normal electrolyte serum concentrations and kidney function. Mean ± SD 25(OH)D concentration was 18.3 ± 8.3 ng/ml. A significant (p<0.001) seasonal variation was seen for both 25(OH)D and PTH. Women were divided into two groups based on their vitamin D status: low vitamin D status (25(OH)D <12 ng/ml, n= 161, 28%) and normal vitamin D status (25(OH)D ≥12 ng/ml, n= 409, 72%). Hypovitaminosis D was found in 38.5% of all the women in the time period December–May and in 12.5% in the other half-year; among women >70 years old 51% had hypovitaminosis D in the time period December–May and 17% in the other half-year. PTH was significantly (p<0.05) increased, and Ca24h, OC and FBMD significantly (p<0.05) decreased in women with hypovitaminosis D. 1,25(OH)₂D positively correlated with 25(OH)D (p<0.0001), but did not correlate with PTH, age or creatinine clearance. In conclusion, hypovitaminosis D is an important, underestimated problem in Italian free-living postmenopausal women referred to an outpatient osteoporosis clinic. Received: 9 February 1998 / Accepted: 8 July 1998     

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.     

The Presence and Severity of Vertebral Fractures is Associated with the Presence of Esophageal Hiatal Hernia in Postmenopausal Women

We examined the relationship between the presence of esophageal hiatal hernia (HH) assessed by endoscopy and the presence of vertebral fractures (VFs) in 87 Japanese postmenopausal women (age range 52–87 years). We found that 29 (63%) of 46 patients with HH (71.2 ± 6.1 years, mean ± SD) had one or more VFs, compared with 14 (34%) of 41 patients without HH (70.8 ± 6.8 years), which was a significant difference in the frequency of VFs (c²= 7.242; p= 0.0071). The average number of VFs per patient was significantly higher for the patients with HH than for those without HH (1.67 ± 1.75 vs 0.68 ± 1.21, p= 0.0032). There were no significant differences in absolute or age-matched bone mineral density (BMD) values at the lumbar spine (0.656 ± 0.131 vs 0.662 ± 0.148 g/cm²; Z-score, –0.35 ± 1.17 vs –0.26 ± 1.00) and there were no significant differences in biochemical parameters, age, years since menopause or body mass index (BMI) between the two groups. When patients were divided into those with reflux esophagitis (RE) (n= 30, 70.2 ± 7.3 years) and those without RE (n= 57, 71.4 ± 5.9 years), no significant differences were detected in any of the above parameters including the presence or number of VFs. The patients were further subdivided into four groups: those with ‘HH only’ (n= 23, 72.3 ± 4.6 years), with ‘RE only’ (n= 7, 70.9 ± 7.7 years), with ‘both’ (n= 23, 70.0 ± 7.3 years) and with ‘neither’ (n= 34, 70.8 ± 6.7 years). One or more VFs were found in 12 (52%), 1 (14%), 17 (74%), and 13 (38%) patients in each group, respectively, and the difference in frequency was significant (c²= 10.748; p= 0.0132). The average number of VFs per patient in each group was 1.57 ± 2.06, 0.14 ± 0.38, 1.78 ± 1.41 and 0.79 ± 1.30, respectively, and there were significant differences between the ‘both’ and ‘neither’ groups, and between the ‘both’ and ‘RE only’ groups (p<0.05). When univariate logistic regression analysis was performed with the presence of HH as a dependent variable and each of the presence of VFs, the number of VFs per patient, absolute or age-matched BMD values at the lumbar spine, BMI and plasma albumin as independent variables, the presence of VFs and the number of VFs per patient were selected as indices affecting the presence of HH (odds ratio: 3.29 and 1.59, 95% confidence interval: 1.36–7.94 and 1.14–2.23; p = 0.0080 and 0.0064, respectively). These results show that the presence and severity of VFs are associated with the presence of HH but not of RE in Japanese postmenopausal women, and suggest that kyphosis induced by multiple VFs might predispose elderly women to a complication with HH. Received: 2 March 2001 / Accepted: 11 June 2001     

Serum 25-hydroxyvitamin D concentrations of New Zealanders aged 15 years and older

Introduction Vitamin D plays an important role in bone health. Our purpose was to measure serum 25-hydroxyvitamin D concentrations and their determinants in a national sample (n=2,946) of New Zealanders aged 15 years and over.Findings Mean (99% CI) serum 25-hydroxyvitamin D concentrations were 47 (45–50) nmol/l in women and 52 (49–55) nmol/l in men. Mean concentrations in New Zealand European and Others (NZEO, n=2,440), Mori (n=370), and Pacific (n=136) were 51 (49–53), 42 (38–46) and 37 (33–42) nmol/l, respectively. Three percent of New Zealanders had serum 25-hydroxyvitamin D concentrations indicative of deficiency (≤17.5 nmol/l); 48% and 84% were insufficient based on cutoffs of ≤50 and ≤80 nmol/l. Determinants of serum 25-hydroxyvitamin D concentrations in women were age, ethnicity, obesity, latitude and season; determinants in men were ethnicity and season. Serum 25-hydroxyvitamin D in women declined with age; mean concentration was 13 (8–18) nmol/l lower in women 65 years or older and 9 (5–13) nmol/l lower in women 45–64 years compared with women 15–18 years. Spring to summer differences in serum 25-hydroxyvitamin D were 31 (28–34) and 28 (25–31) nmol/l in women and men, respectively. Obese women had lower vitamin status than normal-weight women by 6 (3–10). Women living in the South Island had a mean serum 25-hydroxyvitamin D that was 6 (3–9) nmol/l lower than women living in the North Island. Ethnicity and season are the major determinants of serum 25-hydroxyvitamin D in New Zealanders.Conclusion The high prevalence of vitamin D insufficiency in New Zealanders, particularly in older women, may warrant strategies to improve vitamin D status.     

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.     

Bone Metabolism and Gonad Function in Male Patients Undergoing Liver Transplantation: A Two-Year Longitudinal Study

Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48 ± 13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2–L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score <–2.5 SD and the mean BMD was 0.806 ± 0.11 g/cm² (range 0.470–1.045 g/cm²). The BMD was lower 3 months after OLTx and significantly higher 12 and 24 months after OLTx. A significant increase in serum BGP was observed at 6, 12 (p<0.05) and 24 months (p<0.005) after OLTx. The mean serum PTH level was 26.6 ± 3.1 pg/ml at baseline and increased significantly at 12 and 24 months (to 49.4 ± 9.9 and 61.2 ± 10.1 pg/ml, respectively; p<0.05). 25OHD serum levels were low at baseline and returned to the normal range after 12 and 24 months (baseline, 8.73 ± 1.54 ng/ml; 12 months, 16.4 ± 2.6 ng/ml; 24 months, 17.67 ± 3.1 ng/ml; p<0.05). FT was significantly lower at baseline than in a group of 10 healthy controls (5.09 ± 10.99, vs 10.3 ± 1.1 pg/ml; p<0.0001). After OLTx a significant increase in FT was recorded at 6, 12 (p<0.05) and 24 months (p<0.005). FT was not correlated with BMD, however. After OLTx an increase in FSH and LH was observed (but failed to reach statistical significance) at 3 and 6 months, followed by a slight reduction at 12 and 24 months. Thus a high proportion of men with end-stage liver disease do have osteoporosis. After OLTx, an early recovery of gonad function is observed, followed by an increase in bone mass, which occurs from the sixth month onward. Received: 3 October 2000 / Accepted: 21 March 2001     

Vitamin D and Bone Mineral Density in Ambulatory Women Living in Buenos Aires, Argentina

The aim of this study was to determine possible associations between bone mineral density (BMD), 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (PTH). In a retrospective study we examined the case notes of free-living postmenopausal women living in our city (34° S). We also report a low prevalence of vitamin D deficiency (25(OH)D <25 nmol/l, 5.6%) and of secondary hyperparathyroidism (intact PTH >65 pg/ml, 7.5%). Age was correlated with BMD at the lumbar spine (r=−0.25, p = 0.00038) and femoral neck (r=−0.252, p = 0.0003). Body mass index (BMI) was correlated with BMD at the femoral neck (r= 0.177, p = 0.021) but not at the lumbar spine. 25(OH)D was positively correlated with BMD at the femoral neck (r = 0.149, p=0.036) but not at the lumbar spine. PTH was positively correlated with age (r= 0.279, p = 0.012) and negatively correlated with 25(OH)D (r=−0.322, p = 0.0036). PTH was also negatively correlated with BMD at the lumbar spine (r=−0.258, p=0.02) and the femoral neck (r=−0.282, p = 0.011). Forward stepwise multiple regression showed that BMI, age and 25(OH)D made significant contributions to BMD at the femoral neck. PTH also showed a significant contribution to BMD at both sites. In conclusion, weak correlations found between PTH and 25(OH)D and BMD suggest these biochemical variables, among other factors, contribute to lumbar spine and femoral neck BMD. Received: 19 February 2000 / Accepted: 20 June 2000     

The Effect of Intermittent Slow-Release Sodium Fluoride and Continuous Calcium Citrate Therapy on Calcitropic Hormones, Biochemical Markers of Bone Metabolism, and Blood Chemistry in Postmenopausal Osteoporosis

A detailed examination of calcitropic hormones and biochemical markers of bone turnover, serum chemistry, and blood hematology was performed in 75 postmenopausal women allocated to two groups: placebo plus calcium citrate (400 mg Ca B.I.D.) (n = 36) or intermittent slow-release sodium fluoride (SRNaF, 25 mg B.I.D.) plus calcium citrate (n = 39). After 2 years of therapy, a significant reduction in serum immunoreactive parathyroid hormone (PTH) was seen for both groups (43 ± 18 SD–30 ± 11 ng/liter, in placebo and 46 ± 24–36 ± 10, in SRNaF P < 0.0001 for both groups). Serum 1,25(OH)₂D significantly fell in placebo-treated patients (91 ± 31–75 ± 34 pmol/liter, P= 0.001) but did not change for SRNaF-treated patients. This difference in response between placebo and SRNaF-treated groups was significant, P= 0.005. Urinary hydroxyproline significantly declined during treatment in both groups (130 ± 61–76 ± 38 μmol/day, for placebo and 138 ± 84–84 ± 38 for SRNaF, P= 0.001). Similar decreases in urinary N-telopeptide of type I collagen were also observed for both groups (305 ± 192–252 ± 197 nmoles BCE/day for placebo and 356 ± 230–220 ± 197, P= 0.0001 for SRNaF). Serum carboxyterminal propeptide of type I collagen (PICP) declined significantly in both the placebo and SRNaF groups (118 ± 38–101 ± 36 μg/liter, and 116 ± 47–105 ± 39, P= 0.0027). Serum osteocalcin did not change significantly for either group, but bone-specific alkaline phosphatase (BS-ALPase), another marker of bone formation, demonstrated a significant fall in the placebo group at 2 years of therapy (16.2 ± 6.7 U/liter–12.1 ± 3.5, P= 0.009) and a small increase in the SRNaF-treated patients (13.0 ± 4.1–15.0 ± 4.5). The observed difference in response of BS-ALPase between the placebo and treated groups was significant (P= 0.007). There were no significant changes within or between treatment groups for blood hematology or serum chemistries. Mean values for all parameters remained within established normal ranges. These findings suggest that administration of calcium citrate inhibited PTH secretion and thereby reduced bone resorption in both groups, indicated by a decline in serum PTH, urinary hydroxyproline, and N-telopeptide. A low turnover state of bone may have been produced in the placebo group taking calcium citrate alone, since serum PICP, BS-ALPase, and 1,25(OH)₂D also decreased. The addition of SRNaF prevented serum 1,25(OH)₂D from falling by an unknown mechanism. However, its anabolic action on the skeleton was best reflected by changes in BS-ALPase. Moreover, SRNaF appeared to exert no deleterious effects on blood chemistries or hematology during 2 years of administration. Received: 28 January 1996 / Accepted: 25 April 1997     

Incomplete Renal Tubular Acidosis in ‘Primary’ Osteoporosis

Chronic metabolic acidosis may increase alkali mobilization from bone and thus promote the development of osteoporosis. While it is undisputed that overt metabolic acidosis is associated with metabolic bone disease, renal acidification in patients with idiopathic osteoporosis has not been studied systematically. The purpose of this study was to investigate the prevalence of renal acidification defects in patients with ‘primary’ osteoporosis. Thirty-two women (including 10 premenopausal women) and 16 men who were referred to our department for investigation of osteoporosis were enrolled in this study. Patients with obvious or possible secondary osteoporosis were excluded. None of the patients had overt metabolic acidosis. In random urine samples 12 of the 48 patients had pH levels below 5.5 and were therefore considered to have normal renal acidification. The remaining 36 patients underwent further testing by a short-course oral ammonium chloride load. In this test nine of these 36 patients (7 men and 2 premenopausal women) failed to lower urinary pH below 5.5 despite the induction of systemic metabolic acidosis. In these patients, therefore, the diagnosis of incomplete distal renal tubular acidosis was made (RTA I). Patients with incomplete RTA I had significantly lower spontaneous plasma pH (7.38 ± 0.0081 vs 7.41 ± 0.004, mean ± SEM, p= 0.002), a lower serum bicarbonate concentration (21.9 ± 0.49 mmol/l vs 23.1 ± 0.24 mmol/l, p= 0.034), a lower base excess (−2.33 ± 0.42 mmol/l vs −0.55 ± 0.21 mmol/l, p= 0.001) and lower Z-scores in bone densitometry (−2.18 ± 0.27 vs −1.40 ± 0.15, p= 0.028) than patients with normal renal acidification. In conclusion, a high prevalence of incomplete RTA I (in 44% of the male patients, 20% of the premenopausal female patients and 6% of all female patients) was found in patients with osteoporosis who, without testing, would have been diagnosed as having ‘primary’ osteoporosis. The mild metabolic acidosis observed in these patients may have contributed to loss of bone mass by a compensatory mobilization of alkali and calcium from bone. Because of possible therapeutic consequences (e.g., administration of alkali salts and high doses of vitamin D) we propose that measurements of urinary pH and, if necessary, ammonium chloride testing should be included in the diagnostic investigation especially of male and of premenopausal female patients with osteoporosis. Since referral bias, although unlikely, cannot be excluded in our study, the prevalence of RTA I in unselected patients with osteoporosis needs to be determined at primary screening institutions. Received: 23 September 1998 / Accepted: 26 March 1999     

Vitamin D: A Necessity for Children and Adolescents in Greece

Children and adolescents with the high bone turnover comprise a high risk population for vitamin D insufficiency. A sample of 178 clinically healthy children aged 3 to 18 years who came from public schools and lived in North West of Greece participated in the study. They were grouped into three age groups (I: 3–10, II: 11–14 and III: 15–18 years of age). Blood samples were taken during winter and summer months for determining calciotropic hormones, calcium, phosphate and biochemical markers of bone synthesis. A high percentage (47%) of the subjects aged 15–18 years was found to have 25OHD <10 ng/ml in winter but much less (13–14%) of the younger ages (13–14 years), while in the summer they were all >10 ng/ml. The prevalence was even higher in the girls of the older group accompanied by lower Pi concentrations again in winter (win:1.19±0.03, sum:1.93±0.03 mmol/l, p < 0.001). The 24,25(OH)₂D levels were changing in parallel to 25OHD, but again in the older subjects, during winter, they were by 2/3 lower than the summer ones (0.73±0.10 vs. 2.41±0.20 ng/ml, p < 0.001). No significant differences were found between seasons and groups in the 1,25(OH)₂D levels. The biochemical markers of bone synthesis, osteocalcin (OC) and total alkaline phosphatase (ALP), were found significantly lower in the girls of the older group both in winter and summer respectively.Even in a sunny country like Greece the adolescents living in an urban area are in high risk for vitamin D deficiency during winter. Supplementation with vitamin D of milk, of popular beverages and perhaps some foods would be of help.     

Quantitative Ultrasound of the Calcaneus and Falls Risk in the Institutionalized Elderly: Sex Differences and Relationship to Vitamin D Status

Very frail older people constitute an increasing proportion of aging populations and are likely to contribute substantially to costs due to osteoporosis. Quantitative ultrasound (QUS) of the calcaneus is potentially a simple method for assessing fracture risk in frail elderly, but there have been few studies of male/female differences in QUS or its relationship to falls risk or vitamin D status, which is often subnormal in this population. We studied QUS, falls risk and serum 25(OH)-vitamin D in subjects living in institutional aged care facilities (hostels or nursing homes). The study sample comprised 294 men (mean age 81.2 years, range 65–102 years) and 899 women (mean age 86.7 years, range 65–104 years). Broadband ultrasound attenuation (BUA) and velocity of sound (VOS) were higher in men than women by approximately 30% and 2% respectively (p<0.0001) and this difference was maintained at all ages. Serum 25(OH)D levels were higher in men than women (p<0.001) but vitamin D deficiency was very common in both sexes and serum 25(OH)D was not associated with QUS in either sex. There was no significant decline in BUA or VOS with age in men; however, for women BUA declined by 2.8–4.7% per decade and VOS by 1% per decade (both p<0.001). Mean BUA T-scores were −1.55 and −2.48 at age 90 years in men and women. Quadriceps strength and weight but not serum 25(OH)D were significantly associated with BUA. These data suggest only minor loss occurs at the calcaneal site in BUA and VOS with very old age in either sex. Received: 7 March 2002 / Accepted: 5 June 2002 Correspondence and offprint requests to: Professor Philip Sambrook, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Tel: +61 2 9926 7281. Fax: +61 2 9906 1859. e-mail: sambrook@med.usyd.edu.au