Anticonvulsant drug-induced osteomalacia: Alterations in mineral metabolism and response to vitamin D3 administration

Summary Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal⁴⁷Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D₃ was normal. Following 4 months of treatment with vitamin D₃ (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P<0.05); 24-h urinary calcium excretion rose by 98% (P<0.001), and forearm bone mass increased by 5.6% (P<0.05). It is concluded that moderate-dose vitamin D₃ supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.     

Sequential changes in mineral metabolism and serum vitamin D metabolite concentrations produced by phenobarbital administration in the rat

Summary We examined the effect of daily phenobarbital administration on serum vitamin D metabolite levels and indices of vitamin D biologic activity in 7-week-old male rats maintained on parenteral vitamin D supplementation (125 ng/day). Treatment with phenobarbital (75 mg/kg/day) produced a biphasic response in parameters of vitamin D biologic effect, including serum calcium concentration, serum inorganic phosphate concentration, and intestinal⁴⁵Ca calcium absorption. An initial increase in these values, maximal after 3–5 days of treatment, was followed by a subsequent decline to subnormal levels by day 21. A parallel biphasic pattern was observed for serum 25-hydroxyvitamin D (25OHD) concentration. Serum 25OHD reached a peak increase of 87% above control levels (P<0.01), observed after 5 days of treatment, and subsequently declined to 62% of control animal values (P<0.01) by 21 days. Serum 24,25(OH)₂D concentration followed a similar course and exhibited a strong positive correlation with serum 25OHD concentrations (r=0.74,P<0.01). In contrast, serum 1,25(OH)₂D concentration was not significantly different from control values after 5 days but was increased 80% over control values (P<0.05) by day 21. Serum vitamin D concentration declined progressively in treated animals, falling to 50% of control levels (P<0.05) by day 5 and to 27% of control levels (P<0.001) by day 21. At the point of maximal increase in serum 25OHD concentration, hepatic microsomal vitamin D₃-25-hydroxylase activity was not increased in the treated animals whereas hepatic mitochondrial vitamin D₃-25-hydroxylase activity was increased by 2.4-fold. Increased hepatic mitochondrial vitamin D₃-25-hydroxylase activity persisted through 21 days of phenobarbital treatment. It is concluded that phenobarbital administration in the rat produces an initial increase in vitamin D biologic effect which correlates temporally with increased circulating levels of 25OHD, the latter possibly resulting from increased hepatic mitochondrial vitamin D-25-hydroxylase activity. A subsequent decline in serum 250HD concentration may be the result of decreased availability of vitamin D as substrate. This sequence of alterations in vitamin D metabolism bears potentially important implications for the timing of prophylactic vitamin D supplementation in patients treated with anticonvulsant drugs.     

Influence of PTH and 1,25(OH)2D on calcium homeostasis and bone mineral content after gastric surgery

Summary In 57 patients surgically treated for ulcer, we found low 25OHD concentrations, elevated 1,25(OH)₂D concentrations, (P<0.001), a normal iPTH level, and a not significantly reduced bone mineral content (BMC) measured by single photon absorptiometry. The 25OHD concentrations were highest in patients regularly taking tablets containing vitamin D (P<0.05), whereas the 1,25 (OH)₂D concentrations and the BMC values were not affected by vitamin D intake. The most severe calcium metabolic disturbances were seen in 15 Billroth I resected patients whose BMC was 89.4±12.4% of normal. Although the dietary intake of calcium and vitamin D complied with the Scandinavian recommendations and calcium absorption was in the lower part of the normal range, the general state of nutrition appears to influence the bone mass of such patients. In the patients as a group, the 1,25(OH)₂D concentrations were significantly related to BMC (r=0.42,P<0.001) and biochemical signs of bone resorption (r=0.68,P<0.001) and formation (r=0.42,P<0.001) Conversely, no relationship could be detected between serum iPTH and bone mass or bone turnover. We suggest that the high 1,25(OH)₂D concentrations found after gastric resections express a compensatory process leading to an increase in calcium absorption, and that the initial event in this sequence is a trend toward low serum calcium levels. With increased demands on this regulation or lack of precursor for 1,25(OH)₂D synthesis, bone mass declines through the action of 1,25(OH)₂D and/or PTH.     

Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women

OBJECTIVES: To determine factors influencing serum 25 hydroxyvitamin D (25OHD) concentration and relationships between serum 25OHD concentration, bone turnover markers, bone mineral density (BMD), and vitamin D receptor (VDR) genotype in Emirati women. METHODS: Serum 25OHD, parathyroid hormone (PTH), osteocalcin (OC), vitamin D binding protein (VDBP), and urinary deoxypyrdinoline (UDPD) concentrations and VDR genotype were determined in Emirati women volunteers who were participating in a study aiming at establishing a reference database for BMD. RESULTS: Serum 25OHD concentration in the 259 women volunteers was 25.3 +/- 10.8 nmol/l (mean +/- SD), and all had vitamin D deficiency (25OHD <80 nmol/l). Mean serum 25OHD was highest in April (29.2 +/- 13.0 nmol/l), which marks the end of the short and cooler winter season, and lowest in August (18.2 +/- 5.9 nmol/l). No significant difference in 25OHD concentration was noted among Emirati women wearing different dress styles, but the mean serum 25OHD was significantly lower in comparison with non-Arab Caucasian women volunteers who dressed in a Western style (P < 0.001). Serum 25OHD correlated positively with age (r = 0.2), number of pregnancies (r = 0.16), dietary vitamin D intake (r = 0.15), serum calcium (r = 0.14), phosphorus (r = 0.14), VDBP (r = 0.15), and urinary calcium/creatinine (r = 0.2), and inversely with PTH (r = -0.22), OC (r = -0.13), and UDPD/creatinine (r = -0.15); P < 0.05 for all correlations. Multiple linear regression analysis showed that age, dietary vitamin D intake, multivitamin intake, and cooler season were independent positive predictors of serum 25OHD concentration (R(2) = 0.18). The frequencies of VDR genotypes were 36% GG, 44.1% AG, and 19.9% AA. Allele frequencies were 58% for G allele and 42% for A allele and were in Hardy-Weinberg equilibrium (x(2) = 1.44; P > 0.1). There was no statistically significant influence of VDR genotype on bone turnover or BMD. CONCLUSIONS: Vitamin D deficiency is highly prevalent in Emirati women and appears largely attributable to insufficient sunlight exposure. It is associated with increased bone turnover. VDR genotype does not appear to influence bone turnover markers or BMD in Emirati women.     

Immobility as a Major Cause of Bone Remodeling in Residents of a Long-Stay Geriatric Ward

Residents of a long-stay geriatric ward at the University Hospital Basel were included in a study to investigate the effects of hypovitaminosis D and immobility. All 91 women (mean age 82.5 years) and 92 men (mean age 78.7 years) were enrolled in the study. Measurements included bone resorption, as measured by urinary deoxypyridinoline (dpd), serum 25-hydroxyvitamin D (25OHD), serum intact parathyroid hormone (iPTH), and their correlations with a four grade mobility score. Mobility score reflected the degree of weight bearing, ranging from walking independently to primarily bed bound. In 86% of all residents, serum 25OHD levels were below the normal limit of 12 ng/ml. Secondary hyperparathyroidism (HPT) was detected in 24% of all patients, using 55 pg/ml as the upper limit for serum iPTH. No significant correlation was found between urinary dpd and serum 25OHD or serum iPTH. Mobility index and both urinary dpd (f: P= 0.001, r = 0.37; m: P < 0.0001, r= 0.47) and serum calcium (female: P= 0.007, r = 0.28; male: P= 0.02, r= 0.24) were positively related. In institutionalized elderly people with a high prevalence of vitamin D deficiency serum intact PTH levels did not correlate with bone resorption as measured by urinary deoxypyridinolin. However, more immobile subjects had significantly higher excretion rates for urinary dpd and higher serum calcium levels. Our results suggest that in elderly people immobility may contribute to bone loss that might preempt the development of secondary HPT through elevation of serum calcium. Received: 12 February 1998 / Accepted: 1 November 1998     

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     

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.     

Vitamin D and Skeletal Growth and Development

Vitamin D is critical to bone mineral metabolism and to the growth and development of the skeleton. Optimizing vitamin D status could be one of the cornerstones to optimize skeletal growth and achieving the maximum peak bone mass soon after the completion of adolescence. Maximizing peak bone mass is considered to be the key to primary prevention of osteoporosis. There is controversy, however, about what constitutes a healthy vitamin D status based on the most abundant circulating metabolite of vitamin D, namely 25 hydroxyvitamin D (25 OHD) in plasma or serum; and even the value of 25 OHD that should be used to define vitamin D deficiency. We reviewed the recent data on circulating 25 OHD concentrations and its relationship with skeletal growth in apparently healthy children and in those with nutritional vitamin D deficiency.     

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.     

Association between vitamin D status and serum parathyroid hormone concentration and calcaneal stiffness in Japanese adolescents: sex differences in susceptibility to vitamin D deficiency

There is currently insufficient information on serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and bone mineral status in healthy adolescents to allow reference values to be set. This study aimed to provide comparable data on vitamin D status in Japanese adolescents and to assess sex differences in susceptibility to vitamin D insufficiency. Serum 25OHD and PTH concentrations were measured in 1,380 healthy adolescents (aged 12–18 years). Subjects completed a questionnaire on exercise history, diet, and lifestyle factors. Calcaneal stiffness was evaluated by quantitative ultrasound. Serum 25OHD concentrations in boys and girls were 60.8 ± 18.3 and 52.8 ± 17.0 nmol/L, respectively. Approximately 30 % of boys and 47 % of girls had suboptimal 25OHD concentrations (<50 nmol/L). Serum PTH concentration was negatively correlated with serum 25OHD concentration in boys, but negatively correlated with calcium intake rather than serum 25OHD in girls. In contrast, the increment in calcaneal stiffness as a result of elevation of serum 25OHD was higher in girls than in boys. As vitamin D deficiency is common in Japanese adolescents, it was estimated that intakes of ≥12 and ≥14 μg/day vitamin D would be required to reach 25OHD concentrations of 50 nmol/L in boys and girls, respectively. Moreover, the results of the present study indicate that vitamin D deficiency has a greater association with calcaneal stiffness in girls than in boys.     

Mineral Metabolism in Obese Patients Following Vertical Banded Gastroplasty

Background Bone disease has been described in patients after surgical treatment for obesity, but few studies have dealt with the impact of vertical banded gastroplasty on mineral metabolism. We have examined bone mineral metabolism in morbidly obese patients before and after 3 months after vertical banded gastroplasty without vitamin D supplementation. Methods Sixteen morbidly obese patients (14 women, 2 men) with a mean (±SD) age of 38 ± 9 years and a body mass index (BMI) of 47.1 ± 8.1 kg/m² were studied. No vitamin D supplementation was given. Body weight, fat mass, calcium, 25OHD, iPTH, bone remodeling markers, and leptin levels were measured at baseline and after weight loss. Results Mean weight loss was 28 ± 11 kg; BMI and body fat mass decreased by 20 and 35%, respectively. Bone resorption markers and albumin-corrected serum calcium increased after operation, whereas iPTH fell. Serum 25OHD levels rose. Leptin levels decreased. Serum iPTH was positively correlated with weight, BMI, and fat mass before operation (p < 0.05), and its decline after weight reduction was negatively associated with the increase in bone resorption markers (p < 0.01). Leptin concentration was correlated with BMI and body fat mass (p < 0.05) both before and after surgery. Conclusions Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.     

Hypovitaminosis D osteopathy: is it mediated through PTH, lean mass, or is it a direct effect?

Hypovitaminosis D is increasing worldwide and is associated with low bone mass. The effects of hypovitaminosis D on bone might be direct or mediated through decreased muscle mass and function and/or secondary hyperparathyroidism. This study systematically investigated the relative contribution of lean mass, PTH, and the direct effect of vitamin D as predictors of vitamin D mediated osteopathy in elderly individuals. 460 ambulatory subjects aged 65-85 years had their bone mass and lean body mass measured by a dual-energy X-ray absorptiometry. Serum calcium, phosphorus and alkaline phosphatase, intact parathyroid hormone (PTH) and 25-hydroxyvitamin D (25 OHD) were also measured. Serum 25 OHD correlated with lean body mass in men, r = 0.24, P = 0.002, but not in women; and with bone mass at all skeletal sites in men, r = 0.20-0.30, P < 0.02. Correlations were also noted at all skeletal sites in women except for the spine, r = 0.13-0.18, P < 0.04. In both genders, BMD at sites enriched in cortical bone was 0.4-0.7 SD lower in the group with the lowest vitamin D tertile than that in the group in the highest tertile. After controlling for PTH, the magnitude of the correlations between BMD and 25 OHD remained significant in both genders. After controlling for lean body mass, the magnitude of these correlations did not change in women and decreased but remained significant in men. After adjustment for age and height, both lean body mass and PTH had significant independent contributions to BMD variance at all skeletal sites. After adjustment for age, height, lean mass, and PTH, 25 OHD did not have any significant residual contribution to BMD variance except at the trochanter in men. This study demonstrates that vitamin D osteopathy in the elderly is in large part mediated through lean mass in men and through PTH levels in both genders, with a greater contribution of PTH in women than in men. There was little demonstrable independent relation between serum 25 OHD and bone mass.     

Postoperative tetany in Graves disease: important role of vitamin D metabolites

OBJECTIVE: To test the authors' hypothesis of the causal mechanism(s) of postoperative tetany in patients with Graves disease. SUMMARY BACKGROUND DATA: Previous studies by the authors suggested that postoperative tetany in patients with Graves disease occurs during the period of bone restoration and resulted from continuation of a calcium flux into bone concomitant with transient hypoparathyroidism induced by surgery. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and bone metabolic markers in 109 consecutive patients with Graves disease who underwent subtotal thyroidectomy. RESULTS: Preoperative serum iPTH levels negatively correlated with ionized calcium levels and positively correlated with 1,25(OH)2D or 1,25(OH)2D/25OHD. After the operation, there was a significant decline in levels of ionized calcium, magnesium, and iPTH. Serum iPTH was not detected in 15 patients after surgery. Four of these 15 patients, and 1 patient whose iPTH level was below normal, developed tetany. Preoperative serum ionized calcium levels were significantly lower, and iPTH levels were higher, in the 5 patients with tetany than in the 11 patients who did not develop tetany despite undetectable iPTH levels. The tetany group had significantly lower serum 25OHD levels and higher 1,25(OH)2D levels, and had increased 1,25(OH)2D/25OHD as an index of the renal 25OHD-1-hydroxylase activity than those in the nontetany group. These results suggest that patients with a high serum level of iPTH as a result of low serum calcium levels (secondary hyperparathyroidism) are susceptible to tetany under conditions of hypoparathyroid function after surgery. CONCLUSIONS: Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a relative deficiency in calcium and vitamin D because of their increased demand for bone restoration after preoperative medical therapy concomitant with transient hypoparathyroidism after surgery. Calcium and vitamin D supplements may be recommended before and/or after surgery for patients in whom postoperative tetany is expected to develop.     

Longitudinal Study of Bone Density and its Determinants in Women in Peri- or Early Menopause

The evolution of bone mass across menopause as well as the factors related to bone loss were studied in 141 women already assessed 10 years ago while in premenopause. Bone density of the lumbar spine was measured by dual photon absorptiometry. Nutrient intakes, lifestyle habits, data on menopause, and hormone replacement therapy were obtained by questionnaires. Present bone density was related significantly to past and current calcium intake, current vitamin D intake, and leisure physical activity level, as well as bone density measured in premenopause. Average bone loss was related to time elapsed without estrogens, age at menopause and present age, as well as serum levels of osteocalcin and alkaline phosphatase (ALP). Bone loss was inversely related to calcium and vitamin D intakes and to serum 25-OH vitamin D (25OHD) levels. By multiple regression analyses, only bone density in premenopause, time without estrogens, weight, vitamin D intake, and serum ALP levels remained as independent predictors of present bone mass or bone loss. This study emphasizes the importance of building a good bone mass before menopause, of having adequate vitamin D intake, and of beginning estrogen replacement therapy as soon as possible to minimize bone loss in the first years of menopause. Received: 21 December 1999 / Accepted: 13 June 2000 / Online publication: 22 September 2000     

High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease

Patients with Alzheimer’s disease (AD) are at increased risk for falls and hip fractures. To better understand causes and prevention, we measured bone mineral density (BMD) in the second metacarpals of 46 ambulatory elderly women with AD and analyzed its relation to serum biochemical indices, sunlight exposure, and vitamin D intake. BMD was significantly less than in age-matched controls. In 26% of AD patients, the serum 25-hydroxyvitamin D (25-OHD) concentration was at a deficient level (5–10 ng/mL), and in 54% it was at an osteomalacic level (<5 ng/mL). Concentrations of ionized calcium were significantly lower in patients. Conversely, concentrations of serum bone Gla-protein and urinary hydroxyproline in patients were significantly higher than in controls. BMD correlated positively with 25-OHD concentration (p = 0.0041) and negatively with parathyroid hormone (PTH) concentration (p = 0.0022). PTH was higher in patients than in controls, and correlated negatively with 25-OHD (p < 0.0001). Many AD patients were sunlight-deprived and consumed less than 100 IU of vitamin D per day. We concluded that vitamin D deficiency due to sunlight deprivation and malnutrition, together with compensatory hyperparathyroidism, contributes significantly to reduced BMD in AD patients. Low BMD increases risk of hip fractures in patients with AD, but may be improved by vitamin D supplementation.     

Suppression of C-Terminal Telopeptide in Hypovitaminosis D Requires Calcium as Well as Vitamin D

We compared the effects of oral calcium and vitamin D separately and together on relevant variables in 22 postmenopausal volunteers with initial serum 25OHD levels below 60 nmol/L. Subjects were allocated randomly to two regimens: group 1 received 1 week of calcium 1,000 mg, followed by 7 weeks with additional vitamin D₃ 1,000 i.u. daily; group 2 received 7 weeks of D₃ 1,000 i.u. daily, followed by 1 week with additional calcium 1,000 mg. We measured serum calcium, phosphate, PTH, 25OHD, CTX, and ALP at baseline and after 1 and 8 weeks in group 1 and after 7 and 8 weeks in group 2. There were no significant changes in ALP from either vitamin D or calcium. Calcium caused significant elevation of serum 25OHD as well as major suppression of serum CTX, which could not easily be accounted for by suppression of PTH. Vitamin D caused no significant change in any variable except elevation of serum 25OHD. The suppressive effect of calcium (whether given first or second) on serum CTX was threefold greater than that of vitamin D (whether given first or second) (P < 0.001), although their suppressive effects on serum PTH were the same. Calcium and vitamin D yielded greater and more significant effects on all variables (except ALP) than either treatment alone. We suggest that calcium may elevate serum 25OHD by prolonging its half-life and that it may have an inhibitory effect on bone resorption independent of, or in addition to, its suppression of PTH.     

Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women

Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25‐hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal‐weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high‐performance liquid chromatography (HPLC) and body composition by dual‐energy X‐ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty‐six women were enrolled. Serum 25OHD was similar between groups (OB 27 ± 2 versus C 26 ± 2 ng/mL; p = 0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34 ± 9 versus C 26 ± 12 ng/g; p = 0.63) or OM compartments (OB 51 ± 13 versus C 30 ± 18 ng/g; p = 0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3 ± 0.6 versus 0.4 ± 0.8 mg, respectively; p < 0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research.     

Increased circulating levels of γ-carboxyglutamic acid-containing protein and decreased bone mass in children on anticonvulsant therapy

Summary In order to investigate the pathophysiology of anticonvulsant-induced osteopenia, circulating levels of bone γ-carboxyglutamic acid-containing protein (Bone Gla Protein: BGP) and urinary excretion of BGP were measured in 16 chidren on chronic anticonvulsant therapy and in 12 control children. Using microdensitometry analysis, osteopenia was found in 25% of the anticonvulsant therapy group, but it was not observed in the control group. Serum BGP and A1-P levels were significantly increased in the anticonvulsant group compared with the control group (P<0.05 andP<0.01, respectively), and a positive correlation was found between serum BGP and A1-P levels (P<0.05). Urinary excretion of BGP and hydroxyproline showed an increase in the anticonvulsant group, but it was not statistically significant. On the other hand, there was no significant difference between the two groups in serum levels of vitamin D metabolites, PTH, calcitonin, Ca, or P or in urinary excretion of Ca or P. It is suggested, therefore, that the increased BGP level in children receiving anticonvulsant therapy is a reflection of high bone turnover due to anticonvulsant drug complications.     

Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2–4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2-–5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2–4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.     

Effects of Postmenopausal Hormone Replacement Therapy With and Without Vitamin D3 on Circulating Levels of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D₃ on vitamin D metabolites (25OHD and 1,25(OH)₂D) were studied in a population-based prospective 1-year study. The serum concentrations of intact parathyroid hormone (PTH), calcium, and phosphate were also studied. A total of 72 women were randomized into four treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), Vit D₃ group (vitamin D₃ 300 IU/day + calcium lactate 500 mg/day), HRT + Vit D₃ group (both above) and placebo group (calcium lactate 500 mg/day). Serum samples were taken in March–April, when vitamin D formation from sunlight in Finland is minimal after the dark winter. Serum concentrations of 25OHD increased in the Vit D₃ group (33.5%, P < 0.001) and in the HRT + Vit D₃ group (38.2%, P < 0.001) but had not changed significantly in the HRT and placebo groups at the 1-year follow-up examination. Serum concentrations of calcitriol (1,25(OH)₂D) increased, however, only in the HRT group (23.7%, P < 0.05), and remained unchanged in other groups. Serum concentrations of PTH decreased by 23.2% (P < 0.05) in the placebo group, but did not change significantly in the other three groups. The concentrations of serum calcium increased in the nonhormone groups (P < 0.001), whereas serum phosphate concentrations decreased in the hormone groups (P < 0.05 and 0.001). Our results confirm the positive effect of 1 year of HRT on serum calcitriol. Vitamin D₃ supplementation increased 25OHD concentrations, but did not affect calcitriol concentrations even though the initial levels were low. Interestingly, the combination of HRT and vitamin D₃ did not increase serum calcitriol concentrations as much as HRT alone. Received: 14 June 1996 / Accepted: 17 June 1997