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PubMed2005

Estimates of optimal vitamin D status.

Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D(3 )to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

Adult↗
PubMed2005

Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus.

Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility.

Absorptiometry, Photon↗
PubMed2005

The relationship of vitamin D status to bone mineral density in an Italian population of postmenopausal women.

Several authors have found a relationship between vitamin D status and bone mineral density (BMD). To our knowledge, no previous studies on this topic have been carried out on the Italian postmenopausal population. We studied this relationship retrospectively in 156 Italian postmenopausal women. We also investigated the relationship between parathyroid hormone (PTH) and BMD. Measurements of BMD were taken at the lumbar spine and upper femur by dual X-ray absorptiometry. Serum 25(OH)D (calcidiol), 1,25(OH)2D (calcitriol), PTH, calcium, phosphorus, creatinine, osteocalcin and urinary calcium and phosphorus were measured according to the current laboratory methods of analysis. We found a positive statistically significant correlation between BMD, both at the spine and hip, and 25(OH)D, and a negative statistically significant correlation between BMD and PTH. No statistically significant correlation was found between BMD and 1,25(OH)2D. Crude logistic regression showed age, 25(OH)D and PTH were significant predictors of low BMD, while 1,25(OH)2D was not. Backward logistic regression showed 25(OH)D was the best predictive model for spine osteoporosis together with age, and on its own it was the best predictive model for femoral neck osteoporosis.

Absorptiometry, Photon↗
PubMed2005

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.

Activities of Daily Living↗
PubMed2005

Absorption of the oral bisphosphonate alendronate in osteoporotic patients with Crohn's disease.

The absorption of bisphosphonates from the gut is poor. The question arises whether the absorption of alendronate, and thus its bioavailability, is further altered by the local inflammatory process in patients with Crohn's disease, thereby potentially affecting clinical outcome when used in the treatment of osteoporosis. To address this question, urinary excretion of alendronate was evaluated 3 months and 6 months after start of treatment with oral alendronate at a dose of 10 mg/day in 19 osteoporotic patients with stable Crohn's disease, 12 of whom had an intestinal resection. Biochemical parameters of bone turnover and BMD were also measured at start and at 6 months. Thirteen patients had been previously treated with glucocorticoids and five were currently using them. The average 24-h urinary excretion of alendronate was 0.5-0.6% of the dose administered, a figure comparable to that reported for osteoporotic patients without gut pathology. There was a significant decrease from baseline in urine N-telopeptides of collagen cross-links (NTx)/creatinine (60%) associated with an increase in lumbar spine BMD of already 2% after 6 months of treatment. Our data suggest that in patients with Crohn's disease, alendronate is adequately absorbed from the intestine and retained in the skeleton. This adequacy is confirmed by appropriate suppression of bone resorption and increase in lumbar spine BMD. These data hold significant implications for the clinical management of patients with Crohn's disease and osteoporosis.

Absorption↗
PubMed2005

Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men.

In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.

Adult↗
PubMed2005

Determinants of bone mineral density in Chinese men.

Osteoporotic fractures are increasing among Asian populations in both genders, but the risk factors for low bone mineral density (BMD) in Asian men is unclear. To determine the hormonal and lifestyle risk factors for low BMD in Asian men, we studied 407 community-dwelling southern Chinese men aged 50 years and above. Medical history and lifestyle habits were obtained with a structured questionnaire. Dietary calcium and phytoestrogen intake were assessed by a semi-quantitative questionnaire. BMD at the spine and hip were measured by dual-energy X-ray absorptiometry (DXA). Fasting blood was analyzed for 25(OH)D, parathyroid hormone (PTH), total and bioavailable estradiol (bio-E) and testosterone (bio-T). The mean age of the cohort was 68.42+/-10.4 (50-96) years. In the linear regression model, weight, age, body mass index (BMI), bio-E, PTH, cigarette smoking and weight-bearing exercise were significant determinants of total hip BMD. Together they explained 55% of the total variance of hip BMD, with body weight being the most important determining factor. With age and weight adjustment, height, bio-T and flavonoid intake were identified as additional determinants of total hip BMD. Strategies to prevent bone loss and osteoporosis in Asian men should include lifestyle modification and maintenance of hormonal sufficiency.

Absorptiometry, Photon↗
PubMed1997

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 degrees and 51 degrees 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 < or = 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.

Adult↗
PubMed1997

Importance of albumin, 25(OH)-vitamin D and IGFBP-3 as risk factors in elderly women and men with hip fracture.

The relative importance of vitamin D deficiency, secondary hyperparathyroidism, nutritional deficiency and low bone mineral density (BMD) as risk factors for hip fracture is not definitely established. In the framework of a case-control study of risk factors for hip fractures, biochemical markers of bone metabolism and nutrition and femoral BMD data were compared in 136 female and 43 male hip fracture patients, 136 female and 44 male age-matched hospitalized controls, and 47 healthy elderly women (8 men). Patients with hip fracture had lower albumin (-10%) and 25(OH)-vitamin D (25(OH)D; -19%) compared with hospitalized controls, and lower albumin (-28%) and 25(OH)D levels (-52%) compared with the elderly controls. Serum values of IGFBP-3 were also significantly lower (-33%) in hip fracture patients than in community controls. BMD of femoral neck was lower (p < 0.001) in patients than in hospitalized and community controls. In hip fracture patients, parathyroid hormone (PTH) correlated weakly with BMD (neck: r = -0.19, trochanter: r = -0.17; both p < 0.05). When all women were pooled (n = 233), albumin correlated significantly (age-adjusted) with BMD at all sites (neck: r = 0.27, trochanter: r = 0.25; all p < 0.001). Albumin, but not 25(OH)D, also correlated with skinfold thickness (r = 0.19, p < 0.0025) and with body mass index (BMI) (r = 0.14, p < 0.05). Male patients with hip fracture had lower BMD and albumin (both p < 0.001), 25(OH)D (p = 0.02) and IGFBP-3 levels (p < 0.005) compared with the controls. When male patients and controls were pooled together, albumin, skinfold thickness and BMI were significantly correlated with each other, but not with BMD. IGFBP-3 was highly correlated with albumin (p < 0.0001), 25(OH)D (p < 0.005) and, less significantly, with PTH (p < 0.05), but not with BMI or skinfold thickness. IGFBP-3 was significantly correlated with BMD at all sites (neck: r = 0.27, p < 0.05; trochanter: r = 0.40, p < 0.0005). In conclusion, low albumin and low BMD were both important risk factors for hip fracture. Low serum albumin was the strongest independent variable correlated with hip fractures. In men. IGFBP-3 was correlated with BMD. The femoral BMD depended only weakly on PTH and 25(OH)D, but was correlated at all sites with albumin, a non-specific parameter of nutrition and general health.

Aged↗
PubMed1998

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 < or = 0.47 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 micrograms/day for 8 weeks), 25(OH)D3 (10, 20 or 50 micrograms/day for 4 weeks) and 1,25(OH)2D3 (0.5, 1.0 or 1.0 microgram/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 micrograms/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 micrograms/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)2D3 at 0.5 microgram/day would raise serum 1,25(OH)2D by 17 pmol/l.

Adult↗
PubMed1999

An international comparison of serum 25-hydroxyvitamin D measurements.

Vitamin D status is usually assessed by measuring the serum 25-hydroxyvitamin D (25(OH)D) concentration. This mainly depends on sunshine exposure, nutrition and age. Interlaboratory variation may hamper comparison between results from different populations. This study reports cross-calibration of the 25(OH)D assays of five laboratories. In study 1, serum 25(OH)D was measured with three different assays in 104 serum samples from a large vitamin D supplementation study. The mean serum 25(OH)D level was 80% higher when measured by competitive protein binding (CPB) assay than by high-performance liquid chromatography (HPLC), while radioimmunoassay (RIA) gave intermediate values. The highest correlation was observed between RIA and HPLC (r = 0.84, p <0.01). Of the serum 25(OH)D values in the lowest quartile by HPLC, 25% were not recognized by CPB and 21% were not recognized by RIA as belonging to the lowest quartile. In study 2, the five laboratories analyzed serum 25(OH)D in eight serum samples covering the concentration range very low to high, with five different assays. The differences between the mean values for serum 25(OH)D between the laboratories with the highest and lowest values was 38%. The ranking order of individual samples according to the serum 25(OH)D value was very similar in all laboratories. The results show that 25(OH)D values from different laboratories can not be assumed to be comparable unless a careful cross-calibration has been performed.

Aged↗
PubMed1999

Determinants of bone loss in elderly men and women: a prospective population-based study.

While several studies have described the rate and pattern of involutional bone loss in women, far less information is available for men. Furthermore, the roles of lifestyle and body build in determining bone loss rate in both sexes have been largely extrapolated from cross-sectional studies. We addressed this issue in a population-based longitudinal study which sought to ascertain rates of bone loss at the femoral neck and lumbar spine in a cohort of men and women aged 60-75 years at baseline, and to relate this loss to anthropometric and lifestyle variables. We additionally investigated the capacity of biochemical markers of bone turnover to predict bone loss rates in these subjects. Women lost bone at all sites; this ranged from 0.20%/year at the lumbar spine to 1.43%/year at the femoral trochanteric region. By contrast, men lost only 0. 20%/year at the trochanteric region, and gained at the lumbar spine (0.33%/year) and at Ward's triangle (0.27%/year) over the 4-year period. Anthropometric measurements were associated with bone loss in both sexes; lower baseline body mass index (BMI) and a greater rate of loss of adiposity over the follow-up period were both associated with greater bone loss at all proximal femoral sites. These attained statistical significance after Bonferroni correction at the total proximal femur among both men (r = 0.29), p<0.01) and women (r = 0.31, p<0.05). Lifestyle factors associated with lower rates of bone loss (after adjustment for BMI) included alcohol consumption at the femoral neck among women (p = 0.007) and physical activity at the lumbar spine among men (p = 0.05). Serum parathyroid hormone, 25-hydroxyvitamin D and biochemical markers of bone turnover did not predict bone loss after adjustment for adiposity.

Aged↗
PubMed2001

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 degrees S). We also report a low prevalence of vitamin D deficiency (25(OH)D < 25 nmol/1, 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.

Adult↗
PubMed2002

Vitamin D deficiency in guinea pigs: exacerbation of bone phenotype during pregnancy and disturbed fetal mineralization, with recovery by 1,25(OH)2D3 infusion or dietary calcium-phosphate supplementation.

Vitamin D (D) deficiency during human pregnancy appears to disturb fetal growth and mineralization, but fetal development is normal in D-deficient rats and vitamin D receptor gene-ablated mice. We used the guinea pig model to investigate maternal and fetal effects of D deficiency. Pregnant (Pr) and nonpregnant (NPr) animals were fed a D-replete (+D) or D-deficient diet (-D) for 8 weeks. We further studied whether the effects of a -D diet are reversed by continuous 1,25(OH)2D3 infusion (-D+1,25) and/or by a lactose-, Ca- and P-enriched D-deficient diet (-D+Ca/P). Bone analyses included histomorphometry of the proximal tibiae, dual-energy X-ray absorptiometry (DXA), and quantitative computed tomography (QCT) of the femora. Depletion of 25(OH)D3 and 1,25(OH)2D3 levels and the D-deficiency syndrome were more severe in pregnant animals. Indeed, Pr/-D but not NPr/-D guinea pigs were hypophosphatemic, and showed robust increases in growth plate width and osteoid surface and thickness; in addition, bone mineral density on DXA was lower in Pr/-D animals only, which was exclusively in cortical bone on QCT. Bone phenotype was partly normalized in Pr/-D+1,25 and Pr/-D+Ca/P animals. Compared with +D fetuses, -D fetuses had very low or undetectable 25(OH)D3 and 1,25(OH)2D3, were hypercalcemic and hypophosphatemic, and had lower osteocalcin levels. In addition, body weight and total body bone mineral content were 10-15% lower; histomorphometry showed hypertrophic chondrocyte zone expansion and hyperosteoidosis. 1,25(OH)2D3 levels were restored in -D+1,25 fetuses, and the phenotype was partially corrected. Similarly, the fetal +D phenotype was rescued in large part in -D+Ca/P fetuses, despite undetectable circulating 25(OH)D3 and 1,25(OH)2D3. We conclude that pregnancy markedly exacerbates D deficiency, and that augmenting Ca and P intake overrides the deleterious effects of D deficiency on fetal development.

Absorptiometry, Photon↗
PubMed2003

Effect of vitamins D2 and D3 supplement use on serum 25OHD concentration in elderly women in summer and winter.

Vitamin D2 and D3 are generally considered equipotent in humans. A few studies have reported that serum 25OHD levels are higher in vitamin D3- compared with vitamin D2-supplemented subjects. As both vitamin D2 and D3 supplements are commonly used by elderly in United States, in the present study we determined the effect of self-reported vitamin D2 and vitamin D3 supplement use on serum total 25OHD levels according to season in elderly women aged 65-77 years. Serum total 25OHD levels were determined in winter and summer in unsupplemented women ( N = 307) and in women who reported taking vitamin D2 ( N = 56) and vitamin D3 ( N = 55) supplements by competitive protein binding assay. In vitamin D2-supplemented women, the contribution of vitamin D2 and D3 to the mean serum total 25OHD level was assessed by HPLC. In summer, there were no significant differences in the mean total serum 25OHD levels (ng/ml) among the vitamin D2 (32 +/- 2.1), vitamin D3 (36.7 +/- 1.95), and unsupplemented (32.2 +/- 0.95) groups. In winter, the mean serum total 25OHD levels were higher in women on vitamin D2 (33.6 +/- 2.34, P < 0.05) and vitamin D3 (29.7 +/- 1.76, NS) supplements compared with unsupplemented women (27.3 +/- 0.72). In vitamin D2-supplemented women, about 25% of the mean serum total 25OHD was 25OHD2, in both summer and winter. Twelve percent of unsupplemented women and 3.6% of vitamin D-supplemented women had a mean serum total 25OHD level below 15 ng/ml in winter. In elderly subjects, both vitamin D2 and Vitamin D3 supplements may contribute equally to circulating 25OHD levels, with the role of vitamin D supplement use being more predominant during winter.

Aged↗
PubMed1997

Role of alfacalcidiol on bone quality and immunomodulation in autoimmune disease and organ transplantation.

In autoimmune diseases, as well as in organ transplantation, corticosteroids are often an obligatory part of the treatment regimen. The deleterious effect of corticosteroids on bone metabolism is well known, although still controversial [1-3]. It is easier to maintain bone mass than to restore it. Although the treatment of choice for prevention of bone loss is hormone replacement therapy, it cannot always be applied, and for many reasons compliance is low over the world. Alternative strategies to prevent bone loss are now tried out in many centers. Calcitonin and bisphosphonates are well-known antiresorbing drugs, but costs and long-term efficiency for calcitonin and fear for bone toxicity for the bisphosphonates limits their use for prevention. An attractive strategy to prevent osteoporosis is the treatment with alfacalcidiol because it is a natural product with important effects on bone metabolism in physiological and pharmacological dosages. Calcium absorption from the gut and mineralization of the bone matrix are optimalized by alfacalcidiol. The purpose of this paper is to report on our experience with alfacalcidiol concerning bone mass and quality in corticosteroid-induced osteoporosis in experimental animals and on long-term bone quality in autoimmune diseases and organ transplantation. We have studied the effects of alfacalcidiol on bone mass and quality in ovariectomized animals with and without corticosteroids. In these fundamental studies we have found that alfacalcidiol had a profound protective and curative effect not only on bone mass but also on bone quality as tested by mechanical testing, namely, impact torsional loading test of whole bones. The combination of alfacalcidiol with estrogens was less effective than alfacalcidiol, but more effective than estrogens alone [4-6] (Fig. 1).

Autoimmune Diseases↗
PubMed1997

Calcitonin, etidronate, and calcidiol treatment in bone loss after cardiac transplantation.

Cardiac transplantation is associated with severe bone loss caused by glucocorticoids, immunosuppressive treatment, and other factors. Treatment protocols for the prevention of bone loss is being studied. Forty patients who underwent cardiac transplantation were randomly given calcitonin (n = 13; 100 UI/d, nasal route), etidronate (n = 14; cyclical treatment 400 mg p.o./d/2 weeks/3 months), or calcidiol (n = 13; 32,000 IU/weekly) therapy for at least 18 months. Serum parameters (Ca, P, alkaline phosphatase, osteocalcin, intact PTH), urinary calcium, and vertebral mineral density (VMD; L2-L4, DXA Hologic QDR 1000) were measured immediately before treatment and after 6, 12, and 18 months of therapy after cardiac transplantation. Patients with cardiac transplantation had a VMD significantly lower than age and sex-matched Spanish controls. Prevalence of osteoporosis (Z-score below -2 SD) was 30%. Osteocalcin levels increased at 6, 12, and 18 months of treatment in the three groups. After 18 months of treatment, VMD increased significantly in the calcidiol 4.9%, vs. -1.19% and -0.19% in the calcitonin and etidronate groups, respectively. A lower incidence of fracture was found in patients treated with calcidiol during the study. In summary, we have found in this open randomized study that calcidiol was the most effective drug in the prevention and treatment of bone loss in patients after cardiac transplantation.

Alkaline Phosphatase↗
PubMed1997

Factors associated with cortical and trabecular bone loss as quantified by peripheral computed tomography (pQCT) at the ultradistal radius in aging women.

Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70-87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of -0.41% and -0.65% per year, respectively. To investigate the mechanism of this age-related decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D3, and PTH (1-84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH)2D3 did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1-84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss.

Aged↗