Positive association between serum 25‐hydroxyvitamin D level and bone density in osteoarthritis

Objective

To describe the association between serum 25‐hydroxyvitamin D (25[OH]D) level and bone mineral density (BMD) in persons with primary knee osteoarthritis (OA).

Methods

We conducted a population‐based survey of the Framingham Study. A total of 228 subjects with primary radiographic knee OA were identified. For vitamin D status, 25(OH)D levels ≤15 ng/ml were classified as vitamin D deficient, 25(OH)D levels 16–32 ng/ml were classified as hypovitaminosis D, and 25(OH)D levels >32 ng/ml were classified as vitamin D replete. We compared average BMD between categories of 25(OH)D levels in subjects with OA using a linear regression model while adjusting for sex, age, body mass index (BMI), knee pain, physical activity, cohort, and disease severity.

Results

Mean age was 74.4 years and 36% were men. Of 228 individuals, 15% were vitamin D deficient, 51% had hypovitaminosis D, and 34% were vitamin D replete. Compared with subjects with vitamin D deficiency, those with hypovitaminosis D had a 7.3% higher BMD (adjusted percent difference; P = 0.02) and vitamin D replete subjects had an 8.5% higher BMD (adjusted percent difference; P = 0.02; test for trend across categories: P = 0.04).

Conclusion

We observed a significant positive association between serum 25(OH)D and BMD in individuals with primary knee OA, independent of sex, age, BMI, knee pain, physical activity, and disease severity. Given the high prevalence of low 25(OH)D status in persons with knee OA and the positive association between 25(OH)D and BMD, vitamin D supplementation may enhance BMD in individuals with OA.

     

Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies

OBJECTIVE: To confirm reports that 25-hydroxyvitamin D (25[OH]D) deficiency is associated with an increased risk of joint space narrowing or cartilage loss in osteoarthritis (OA). METHODS: We measured 25(OH)D levels in subjects from 2 longitudinal cohort studies, the Framingham Osteoarthritis Study and the Boston Osteoarthritis of the Knee Study (BOKS). In the first, weight-bearing anteroposterior (AP) and lateral knee radiographs were obtained on subjects in 1993-1994 and again in 2002-2005 (mean interval 9 years); blood was drawn for measurement of vitamin D status in 1996-2000. In the second, subjects with symptomatic knee OA participating in a natural history study had fluoroscopically positioned semiflexed posteroanterior (PA) and lateral radiography of both knees and magnetic resonance imaging (MRI) of the more symptomatic knee performed at baseline and at 15 and 30 months. Blood was drawn at all visits, and the baseline specimen was used when available. In both studies, we defined radiographic worsening based on joint space loss in the tibiofemoral joint on either AP/PA or lateral weight-bearing views, using a semiquantitative scale (worsening defined as increase by > or =1 on a 0-3 scale). In the BOKS, we evaluated cartilage loss semiquantitatively, using the Whole-Organ Magnetic Resonance Imaging Score. In both studies, 25(OH)D levels were measured by radioimmunoassay. Analyses focused on whether vitamin D levels, defined in tertiles or as deficient (25[OH]D <20 ng/ml) versus nondeficient, predicted worsening of OA. Logistic regression analysis adjusted for age, body mass index, sex, and baseline OA level was used. RESULTS: The 715 subjects in the Framingham Study had a mean 25(OH)D level of 20 ng/ml at baseline, and 20.3% of the knees showed worsening, during the course of the study, with most knees having had no evidence of OA at baseline. The 277 subjects with OA in the BOKS had a mean 25(OH)D level of 20 ng/ml at baseline with 23.6% of knees showing radiographic worsening. We found no association of baseline 25(OH)D levels with radiographic worsening in either cohort, and confidence limits in the analyses of vitamin D deficiency were narrow, suggesting that results were not based on insufficient power. In fact, the risk of worsening was slightly, but not significantly, lower in persons with low levels of vitamin D than in persons with higher levels. In the BOKS, vitamin D levels were unrelated to cartilage loss seen on MRI. CONCLUSION: The findings indicate that vitamin D status is unrelated to the risk of joint space or cartilage loss in knee OA.     

Association of 25‐hydroxyvitamin D with prevalent osteoarthritis of the hip in elderly men: The osteoporotic fractures in men study

Objective

To examine the cross‐sectional association of serum levels of 25‐hydroxyvitamin D, or 25(OH)D, with prevalent radiographic hip osteoarthritis (OA) in elderly men.

Methods

In a cohort of 1,104 elderly men from the Osteoporotic Fractures in Men Study, 25(OH)D serum levels were determined by mass spectrometry, followed by pelvic radiographs ∼4.6 years later. Categories of vitamin D levels were defined as follows: deficiency as ≤15 ng/ml, insufficiency as 15.1–30 ng/ml, and sufficiency as >30 ng/ml. Radiographs were assessed for severity of hip OA using a summary grade of 0–4 for individual features of hip OA. Logistic regression was used to assess associations of serum 25(OH)D levels with prevalent radiographic hip OA; covariates included age, clinic site, season at the time of blood withdrawal, self‐reported hip pain for >30 days, timed 6‐meter walk, presence of at least 1 coexisting condition, and self‐rated health status.

Results

Men with radiographic hip OA had a slower 6‐meter walking time (P < 0.0001), reported more hip pain (P = 0.0001), had a lower vitamin D level (P = 0.0002), and had a higher prevalence of vitamin D insufficiency (P = 0.002) and vitamin D deficiency (P = 0.012) compared with controls. Higher 25(OH)D levels were associated with a lower prevalence of radiographic hip OA (odds ratio [OR] 1.39 per 1 SD decrease in 25[OH]D, 95% confidence interval [95% CI] 1.11–1.74) after adjusting for age, season, and clinic site. Men with vitamin D insufficiency had an increased likelihood of prevalent radiographic hip OA (OR 2.19, 95% CI 1.21–3.97) compared with men with sufficient levels of 25(OH)D, and in men with vitamin D deficiency, there was a tendency toward an increased likelihood of radiographic hip OA (OR 1.99, 95% CI 0.83–4.74).

Conclusion

Men with vitamin D deficiencies are twice as likely to have prevalent radiographic hip OA, and therefore vitamin D therapy to augment skeletal health in the elderly is warranted.

     

Vitamin D in “early” primary Sjögren’s syndrome: does it play a role in influencing disease phenotypes?

Beyond its well-established role in the maintenance of mineral homeostasis, 25-OH-vitamin D deficiency seems to be involved in the development and severity of several autoimmune diseases. To date, contrasting data have been reported regarding the presence of hypovitaminosis D in primary Sjögren’s syndrome (pSS). To assess the prevalence of hypovitaminosis D in pSS at an early stage of the disease and to evaluate its impact on pSS clinical manifestations and disease activity, unselected consecutive subjects with recent onset dry mouth and/or dry eyes who underwent a comprehensive diagnostic algorithm for pSS (AECG criteria) were prospectively included in the study. The levels of 25[OH]-D3 were measured by monoclonal antibody immunoradiometric assay. Conditions of 25[OH]-D3 severe deficiency, deficiency, and insufficiency were defined as levels <10, <20, and 20–30 ng/ml, respectively, and their frequencies were investigated in pSS patients and controls. The levels of 25[OH]-D3 were also correlated with patients’ demographic, clinical, and serologic features. Seventy-six consecutive females were included: 30/76 patients fulfilled the AECG criteria for pSS. The remaining 46/76 patients represented the control group. No statistical differences were found in the serum levels of 25[OH]-D3 between pSS patients [median levels = 20 ng/ml (IQR 9.3–26)] and controls [median levels = 22.5 ng/ml (IQR 15.6–33)]. In particular, the frequency of 25[OH]-D3 severe deficiency was not significantly different in patients with pSS when compared to controls (23 vs. 17.4 %, p value = 0.24). We found a significant correlation between serum 25[OH]-D3 levels and white blood cells count (r = 0.29, p = 0.01). More specifically, leukocytopenia was significantly associated with 25[OH]-D3 severe deficiency, being documented in 40 % of the subjects with a 25[OH]-D3 severe deficiency and in 11 % of the subjects without a severe vitamin D deficiency (p = 0.02). We did not observe any further association or correlation between hypovitaminosis D and pSS glandular and extra-glandular features. Although the role of hypovitaminosis D in pSS pathogenesis remains controversial, the results of this study encourage the assessment of vitamin D in specific pSS subsets that could mostly benefit from a supplementation.     

Vitamin d deficiency and seasonal variation in an adult South Florida population

Hypovitaminosis D is associated with impaired neuromuscular function, bone loss, and fractures. If a person is not taking a vitamin supplement, sun exposure is often the greatest source of vitamin D. Thus, vitamin D deficiency is not uncommon in the winter, particularly in northern latitudes. Our goal was to establish the prevalence of vitamin D deficiency in south Florida (U.S.), a region of year-round sunny weather. At the end of the winter, 212 men and women attending an internal medicine clinic at a local county hospital were enrolled for measurements of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and PTH; 99 participants returned at the end of summer. The mean (+/-sd) winter 25(OH)D concentration was 24.9 +/- 8.7 ng/ml (62.3 +/- 21.8 nmol/liter) in men and 22.4 +/- 8.2 ng/ml (56.0 +/- 20.5 nmol/liter) in women. In winter, the prevalence of hypovitaminosis D, defined as 25(OH)D less than 20 ng/ml (50 nmol/liter), was 38% and 40% in men and women, respectively. In the 99 subjects who returned for the end of summer visit, the mean 25(OH)D concentration was 31.0 +/- 11.0 ng/ml (77.5 +/- 27.5 nmol/liter) in men and 25.0 +/- 9.4 ng/ml (62.5 +/- 23.5 nmol/liter) in women. Seasonal variation represented a 14% summer increase in 25(OH)D concentrations in men and a 13% increase in women, both of which were statistically significant. The prevalence of hypovitaminosis D is considerable even in southern latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis.     

Vitamin D levels: its relationship to bone mineral density response and disease activity in premenopausal Malaysian systemic lupus erythematosus patients on corticosteroids

Aim: To determine if baseline vitamin D levels would influence the gain in bone mineral density (BMD) in female systemic lupus erythematosus (SLE) patients on corticosteroids (CS) taking bone‐active medication. Method: Premenopausal SLE patients participating in a trial assessing the efficacy of calcium alone, calcitriol and calcium, and alendronate and calcium, on BMD in patients on CS, were studied. Patients were randomly allocated to the treatment groups at the start of the study and followed up for 2 years. Serum 25‐hydroxy vitamin D [25(OH)D] was measured at baseline. Results: Thirty‐eight patients were studied. One (2%) patient had osteoporosis, nine (24%) had osteopenia and all others had normal BMD. The mean baseline 25(OH)D levels were 21.6 ± 4.6 ng/mL (± 1 SD). Twelve (32%) patients had vitamin D deficiency [25(OH)D < 20 ng/mL]. There was a significant negative correlation between SLEDAI scores and 25(OH)D levels, that is, patients with high SLEDAI scores had significantly lower 25(OH)D levels (P = 0.033). Left femoral neck BMD was significantly lower in the deficient compared to insufficient group (P = 0.042). There was a trend toward better BMD gain at 2 years in the vitamin D insufficient compared to the deficient group, which did not reach statistical significance. Conclusion: This study showed that in female SLE patients, low vitamin D levels are associated with higher disease activity and suggests that patients who have higher vitamin D levels have a better BMD response during treatment with bone‐active agents.     

Sickle cell bone disease: response to vitamin D and calcium

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.     

No relationship between vitamin D status and insulin resistance in a group of high school students

Objective: To investigate the effects of vitamin D deficiency on both insulin resistance and risk of metabolic syndrome in children. Methods: The study group consisted of 301 children and adolescents with a mean age of 14.2±1.8 years. Serum 25-hydroxyvitamin D [25(OH)D] levels and insulin resistance indices were evaluated. According to serum 25(OH)D levels, the subjects were classified in 3 groups. Those with levels ≤10 ng/mL were labeled as the vitamin D deficient group (group A), those with levels of 10-20 ng/mL as the vitamin D insufficient group (group B) and those with ≥20 ng/mL as having normal vitamin D levels (group C). Metabolic syndrome was defined according to the International Diabetes Federation consensus. The participants with and without metabolic syndrome were compared in terms of 25(OH)D levels.Results: Mean 25(OH)D level of the total group was 18.2±9.3 (2.8-72.0) ng/mL. Distribution of individuals according to their vitamin D levels showed that 11.6% were in group A, 53.5% in group B, and 34.9% in group C. The proportions of boys and girls in these categories were 22.9% and 77.1% in group A, 36.6% and 63.4% in group B, 54.3% and 45.7% in group C, respectively. There were no significant differences in 25(OH)D levels in the individuals with and without impaired fasting glucose or impaired glucose tolerance. No relationship was observed between insulin resistance/sensitivity indices and vitamin D status (p>0.05). Metabolic syndrome was diagnosed in 12.3% (n=37) of the children. There was also no difference in mean 25(OH)D levels between individuals who had and those who did not have the metabolic syndrome.Conclusion: In our study, no correlations were found between insulin measurements during oral glucose tolerance test and vitamin D deficiency. Nonetheless, more extended studies including vitamin D supplementation and evaluating insulin sensitivity via clamp technique are needed to further elucidate this relationship.Conflict of interest:None declared.     

Association of suboptimal 25-hydroxyvitamin D levels with knee osteoarthritis incidence in post-menopausal Egyptian women

The main aim of this study was to assess the vitamin D status of newly diagnosed knee osteoarthritis (OA) patients. Thirty-six post-menopausal Egyptian females of mean age 54.7 years with knee OA were recruited alongside ten healthy males of mean age 25.8 years. The body mass index of all knee OA patients was calculated, and full patient history was gathered to screen for vitamin D status altering conditions or medication. Total 25-hydroxyvitamin D [25(OH)D] was assessed using HPLC which permitted an individualized assessment of both forms of the vitamin’s metabolite, 25(OH)D2 and 25(OH)D3. Results showed that mean 25(OH)D ± SEM concentrations were 25.0 ± 1.6 ng/mL and 35.4 ± 2.1 ng/mL for female patients and healthy male participants, respectively. Student’s t test statistical comparison yielded a significant result (P = 0.001) when comparing healthy and osteoarthritic participants, and insignificant results when comparing patients of different BMI class, and the different forms of the vitamin’s metabolite (P = 0.184 and 0.335, respectively). The 95 % confidence interval associated with knee OA incidence is 21.9–28.1 ng/mL, which is in the vitamin D insufficiency zone. In Conclusion, suboptimal 25(OH)D levels are associated with knee OA incidence in post-menopausal Egyptian females which further fortifies accumulating evidence.     

Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men

CONTEXT: Although racial and ethnic differences in vitamin D status and bone mineral density (BMD) are recognized, less is known about how differences in vitamin D status impact BMD, especially among men. OBJECTIVE: Our objective was to examine the relation between serum 25-hydroxyvitamin D [25(OH)D] and BMD by race and ethnic group. DESIGN: We conducted a population-based, observational survey. Participants: Participants included 1114 Black, Hispanic, and White men, 30-79 yr of age. Outcomes: We assessed 25(OH)D by a competitive protein binding assay and BMD by dual-energy x-ray absorptiometry. RESULTS: Mean age +/- SD of the 331 Black, 362 Hispanic, and 421 White men was 48 +/- 12.8 yr. Mean 25(OH)D was lower among Black (25.0 +/- 14.7 ng/ml) and Hispanic (32.9 +/- 13.9 ng/ml) men compared with White men (37.4 +/- 14.0 ng/ml, P < 0.01). A higher percentage of both Black (44%) and Hispanic (23%) men had levels of 25(OH)D in the lowest quartile, compared with 11% of White men (P < 0.001). After adjusting for age, height, and weight, only White men showed significant positive correlation between 25(OH)D and BMD (range of correlations, 0.00-0.14). Serum 25(OH)D was not associated with BMD in Black or Hispanic men at any bone site. Results were similar when adjusted for age only. CONCLUSIONS: Our findings confirm substantial racial and ethnic group differences in BMD and serum 25(OH)D in men. Serum 25(OH)D and BMD are significantly related to one another in White men only. This may have implications for evaluation of bone health and supplementation in men with low levels of 25(OH)D. Further understanding of the biological mechanisms for these differences between race and ethnic groups is needed.     

Lipid Accumulation Product and 25-OH-Vitamin D Deficiency in Type 2 Diabetes

BACKGROUND: Emerging data suggest a link between vitamin D (25(OH)D) deficiency, type 2 diabetes (T2D), and visceral adiposity. The lipid accumulation product (LAP), strictly correlated with abdominal fat depots, is proposed as marker of dysfunctional adiposity. AIM: To verify the association between 25(OH)D levels and LAP in T2D. METHODS: Body mass index (BMI), waist circumference (WC), glucose, HbA1c, lipids, and 25(OH)D were assessed in 420 T2D outpatients and in 150 non-diabetic obese with similar anthropometric characteristics. LAP was computed as the product of sex-specific enlarged WC and triglycerides (TG). RESULTS: In T2D patients, 63.0% showed 25(OH)D deficiency (<20 ng/ml) vs. 71.3% in the obese control group. Overweight males showed a higher prevalence of 25(OH)D deficiency (60.3%) than women (48.8%, p < 0.001), while in obese patients this prevalence was not significant. In both genders, 25(OH)D was not significantly associated with HbA1c and fasting glucose. Age-adjusted 25(OH)D levels were inversely correlated with BMI (p < 0.001), WC (p < 0.001), and LAP (p < 0.001) in both genders. Metabolic syndrome presented an odds ratio (OR) for 25(OH)D deficiency of 1.6 (1.1-2.5, p = 0.048) in females and 1.7 (1.2-2.7, p = 0.016) in males, while the highest quartile of LAP showed an OR of 2.1 (1.2-3.6, p = 0.019) in females and 3.2 (1.6-6.5, p = 0.02) in males. A similar trend was observed in the obese control group. CONCLUSIONS: In the presence of excess weight, subjects with and without T2D frequently feature low 25(OH)D levels. Subjects with higher LAP exhibit a high risk of 25(OH)D deficiency, suggesting that dysfunctional adiposity is a worsening factor for vitamin D hypovitaminosis.     

The prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese Black Americans

CONTEXT: Both obesity (body mass index, BMI > or = 30 kg/m2) and Black race are associated with a higher risk of vitamin D deficiency and secondary hyperparathyroidism. We hypothesized the risk of hypovitaminosis D would therefore be extraordinarily high in obese Black adults. OBJECTIVE: To study the effects of race and adiposity on 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (iPTH). DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 379 Black and White adults from the Washington D.C. area. BMI ranged from 19.9 to 58.2 kg/m2. MAIN OUTCOME MEASURES: Prevalence of hypovitaminosis D [25(OH)D < 37.5 nmol/l] and secondary hyperparathyroidism [25(OH)D < 37.5 nmol/l with iPTH > 4.2 pmol/l]. RESULTS: Obese Black subjects had lower mean 25(OH)D, 40.3 (SD, 20.3) nmol/l, compared with obese Whites, 64.5 (29.7), P < 0.001, nonobese Blacks, 53.3 (26.0), P = 0.0025 and nonobese Whites, 78.0 (33.5), P < 0.001. The prevalence of hypovitaminosis D increased with increasing BMI, and was greater (P < 0.001) in Blacks than Whites within all BMI categories examined. Among subjects with BMI > or = 35 kg/m2, 59% of Blacks vs 18% of Whites had hypovitaminosis D (odds ratio 6.5, 95% confidence interval 3.0-14.2). iPTH was negatively correlated with 25(OH)D (r = -0.31, P < 0.0001), suggesting those with hypovitaminosis D had clinically important vitamin D deficiency with secondary hyperparathyroidism. For secondary hyperparathyroidism 35.2% of Blacks met the criteria, compared to 9.7% of Whites (OR 3.6, CI 1.5-98.8). CONCLUSIONS: Obese Black Americans are at particularly high risk for vitamin D deficiency and secondary hyperparathyroidism. Physicians should consider routinely supplementing such patients with vitamin D or screening them for hypovitaminosis D.     

Hypovitaminosis D in type 2 diabetes mellitus: Association with microvascular complications and type of treatment

The prevalence of hypovitaminosis D has been recently reevaluated, and diabetes is considered as a risk factor for osteoporosis. We studied the association of the prevalence of hypovitaminosis D with the clinical features of diabetes. We conducted the observational study in 581 Japanese patients with type 2 diabetes mellitus and 51 normal subjects, and analyzed the relationship between serum 25-hydroxyvitamin D (25-OHD) concentration and the clinical features associated with type 2 diabetes. Mean serum 25-OHD concentration in type 2 diabetes patients was 17.0 +/- 7.1 ng/ml (Mean +/- SD) in winter, and was not statistically different from normal population (17.5 +/- 3.6 ng/ml). The prevalence of hypovitaminosis D (<20 ng/ml) was 70.6%. Serum concentrations of 25-OHD were associated with HbA1c (P = 0.013), age (P = 0.070) and serum albumin (P < 0.001), but were not related to BMI or the duration of diabetes. The levels of 25-OHD were significantly lower in the population with apparent microvascular complications, although serum creatinine levels were below 2.0 mg/dl. Serum 25-OHD concentrations in the group treated with insulin (15.4 +/- 6.5 ng/ml) was lower than those in the patients treated with diet alone (20.8 +/- 7.6 ng/ml) and with oral hypoglycemic agents (17.3 +/- 7.0 ng/ml). Furthermore, the highest incidence of osteoporotic fracture and/or back deformity was observed in insulin-treated patients with hypovitaminosis D. In conclusion, these results suggest that microvascular complications and insulin treatment in type 2 diabetes patients are associated with the co-existence of hypovitaminosis D, and that hypovitaminosis D in insulin-treated patients is possibly related to the risk of osteoporotic fracture.     

High-Dose Vitamin D: Helpful or Harmful?

If the optimal serum 25(OH)D level for skeletal health is 30 ng/mL or greater, then vitamin D insufficiency is widespread, affecting about 75% of adults based on a recent survey of more than 20,000 Americans. However, after a comprehensive analysis of existing research studies, the Institute of Medicine recently concluded that nearly all individuals are vitamin D replete when their 25(OH)D levels are 20 ng/mL or greater. Furthermore, two recent publications challenge the belief that 25(OH)D levels greater than 30 ng/mL are optimal for bone health. In a randomized, placebo-controlled trial, high-dose, once-yearly vitamin D therapy increased the incidence of fractures and falls. The second study reported that high-dose vitamin D did not reduce levels of parathyroid hormone or bone resorption among adults with 25(OH)D levels less than 32 ng/mL at baseline. It is time to question whether serum 25(OH)D levels of 30 ng/mL or greater are necessary for all individuals.     

Evidence of hypovitaminosis D in patients with mitral ring calcification

In order to evaluate the role of calcium regulating hormones in the pathogenesis of mitral ring calcification, we have studied the serum levels of PTH and vitamin D metabolites in aged females both with and without mitral ring calcification (MRC). In the patients with MRC (n = 17), significantly lower levels of serum total protein (6.6 +/- 0.2 in the MRC group vs 7.1 +/- 0.1 g/dl in the control group, mean +/- SEM), BUN (15.7 +/- 0.9 vs 18.3 +/- 0.9 mg/dl), creatinine (0.7 +/- 0.02 vs 0.9 +/- 0.02 mg/dl) and calcium (8.4 +/- 0.1 vs 9.2 +/- 0.1 mg/ml) were observed as compared with those in the controls (n = 32). Significantly higher PTH levels (0.57 +/- 0.07 vs 0.38 +/- 0.04 ng/ml) were found in the MRC group. Levels of all three vitamin D metabolites in the MRC group were significantly lower than those in the control group (25-OHD; 11.2 +/- 1.4 vs 19.6 +/- 1.2 ng/ml, 24,25(OH)2D; 0.7 +/- 0.1 vs 1.3 +/- 0.1 ng/ml and 1,25(OH)2D; 12.5 +/- 2.4 vs 43.0 +/- 3.5 pg/ml). The correlation coefficient between PTH and 1,25(OH) 2D was -0.382(n = 49, p less than 0.01). Thus, the significantly higher PTH levels in the MRC group might result in hypovitaminosis D. In conclusion, evidence of hypovitaminosis D in the patients with mitral ring calcification was demonstrated.     

Prevalence of vitamin D deficiency in patients with acute myocardial infarction

Deficiency in 25-hydroxyvitamin D (25[OH]D) is a treatable condition that has been associated with coronary artery disease and many of its risk factors. A practical time to assess for 25(OH)D deficiency, and to initiate treatment, is at the time of an acute myocardial infarction. The prevalence of 25(OH)D deficiency and the characteristics associated with it in patients with acute myocardial infarction are unknown. In this study, 25(OH)D was assessed in 239 subjects enrolled in a 20-hospital prospective myocardial infarction registry. Patients enrolled from June 1 to December 31, 2008, had serum samples sent to a centralized laboratory for analysis using the DiaSorin 25(OH)D assay. Normal 25(OH)D levels are ≥30 ng/ml, and patients with levels <30 and >20 ng/ml were classified as insufficient and those with levels ≤20 ng/ml as deficient. Vitamin D levels and other baseline characteristics were analyzed with the linear or Mantel-Haenszel trend test. Of the 239 enrolled patients, 179 (75%) were 25(OH)D deficient and 50 (21%) were insufficient, for a total of 96% of patients with abnormally low 25(OH)D levels. No significant heterogeneity was observed among age or gender subgroups, but 25(OH)D deficiency was more commonly seen in non-Caucasian patients and those with lower social support, no insurance, diabetes, and lower activity levels. Higher parathyroid hormone levels (45.3 vs 32.7 pg/ml, p = 0.029) and body mass indexes (31.2 vs 29.0 kg/m(2), p = 0.025) were also observed in 25(OH)D-deficient subjects. In conclusion, vitamin D deficiency is present in almost all patients with acute myocardial infarction in a multicenter United States cohort.     

Factors associated with 25-hydroxyvitamin D levels in patients with liver cirrhosis

Introduction. Lower 25-hydroxyvitamin D [25(OH)D] levels have been observed in cirrhotic patients and have been related to disease severity. However, most previous studies included patients with very advanced disease, lacking an adequate control for other variables that could interfere with vitamin D levels. We sought to investigate the prevalence of hypovitaminosis D and the factors related to its occurrence.Material and methods. This cross-sectional study included 133 cirrhotic patients and 30 healthy controls. Bivariate and multivariate analyses were performed to determine factors associated with 25(OH)D levels below the lower tertile. Thirty patients who had been recently hospitalized were compared in two time points.Results. Mean 25(OH)D levels were 32.34 ± 11.38 in controls and 27.03 ± 6.22 ng/mL in patients (P = 0.018). 25(OH)D levels were < 30 ng/mL in 69.9% and < 20 ng/mL in 14.3% of the sample. Levels of 25(OH)D below the lower tertile (< 24 ng/mL) were independently associated with higher triceps skinfold and non-Caucasian race. Parathyroid hormone above the reference value (65 pg/mL) was found in 24.6% of patients without association with 25(OH)D or severity of liver disease. Significantly lower levels of 25(OH)D were found at the time of acute decompensation of cirrhosis.Conclusions. In conclusion, hypovitaminosis D was prevalent in cirrhotics and it was associated with adiposity and non-Caucasian race in stable patients with relatively well preserved liver function. However, significantly lower levels were observed during admission for acute decompensation suggesting an impact of systemic inflammation or liver dysfunction on 25(OH)D levels.     

Treatment of hypovitaminosis D in infants and toddlers

CONTEXT: Hypovitaminosis D appears to be on the rise in young children, with implications for skeletal and overall health. OBJECTIVE: The objective of the study was to compare the safety and efficacy of vitamin D2 daily, vitamin D2 weekly, and vitamin D3 daily, combined with supplemental calcium, in raising serum 25-hydroxyvitamin D [25(OH)D] and lowering PTH concentrations. DESIGN: This was a 6-wk randomized controlled trial. SETTING: The study was conducted at an urban pediatric clinic in Boston. SUBJECTS: Forty otherwise healthy infants and toddlers with hypovitaminosis D [25(OH)D < 20 ng/ml] participated in the study. INTERVENTIONS: Participants were assigned to one of three regimens: 2,000 IU oral vitamin D2 daily, 50,000 IU vitamin D2 weekly, or 2,000 IU vitamin D3 daily. Each was also prescribed elemental calcium (50 mg/kg.d). Infants received treatment for 6 wk. MAIN OUTCOME MEASURES: Before and after treatment, serum measurements of 25(OH)D, PTH, calcium, and alkaline phosphatase were taken. RESULTS: All treatments approximately tripled the 25(OH)D concentration. Preplanned comparisons were nonsignificant: daily vitamin D2 vs. weekly vitamin D2 (12% difference in effect, P = 0.66) and daily D2 vs. daily D3 (7%, P = 0.82). The mean serum calcium change was small and similar in the three groups. There was no significant difference in PTH suppression. CONCLUSIONS: Short-term vitamin D2 2,000 IU daily, vitamin D2 50,000 IU weekly, or vitamin D3 2,000 IU daily yield equivalent outcomes in the treatment of hypovitaminosis D among young children. Therefore, pediatric providers can individualize the treatment regimen for a given patient to ensure compliance, given that no difference in efficacy or safety was noted among these three common treatment regimens.     

Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy

PURPOSE: To evaluate serum 25-hydroxyvitamin D [25(OH)D] concentrations and factors related to vitamin D inadequacy in postmenopausal North American women receiving therapy to treat or prevent osteoporosis. METHODS: Serum 25(OH)D and PTH were obtained in 1536 community-dwelling women between November 2003 and March 2004. Multivariate logistic regression was used to assess risk factors for suboptimal (<30 ng/ml) 25(OH)D. RESULTS: Ninety-two percent of study subjects were Caucasian, with a mean age of 71 yr. Thirty-five percent resided at or above latitude 42 degrees north, and 24% resided less than 35 degrees north. Mean (sd) serum 25(OH)D was 30.4 (13.2) ng/ml: serum 25(OH)D was less than 20 ng/ml in 18%; less than 25 ng/ml in 36%; and less than 30 ng/ml in 52%. Prevalence of suboptimal 25(OH)D was significantly higher in subjects who took less than 400 vs. 400 IU/d or more vitamin D. There was a significant negative correlation between serum PTH concentrations and 25(OH)D. Risk factors related to vitamin D inadequacy included age, race, body mass index, medications known to affect vitamin D metabolism, vitamin D supplementation, exercise, education, and physician counseling regarding vitamin D. CONCLUSIONS: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.     

Serum levels of vitamin D,sunlight exposure,and knee cartilage loss in older adults: The Tasmanian older adult cohort study

Objective

To determine the associations between serum levels of vitamin D, sunlight exposure, and knee cartilage loss cross‐sectionally and longitudinally in older adults.

Methods

A total of 880 randomly selected subjects (mean age 61 years [range 51–79 years], 50% women) were studied at baseline, and 353 of these subjects were studied 2.9 years later. Serum levels of 25‐hydroxyvitamin D (25[OH]D) were assessed by radioimmunoassay, and sunlight exposure was assessed by questionnaire. T1‐weighted fat‐suppressed magnetic resonance imaging (MRI) of the right knee was performed to determine knee cartilage volume and defects. Knee radiographic osteoarthritis (OA) and knee pain were also assessed.

Results

The mean 25(OH)D serum level was 52.8 nmoles/liter at baseline (range 13–119 nmoles/liter). Winter sunlight exposure and serum 25(OH)D level were both positively associated with medial and lateral tibial cartilage volume, and a serum 25(OH)D level <50 nmoles/liter was associated with increased medial tibiofemoral joint space narrowing (all P < 0.05). Longitudinally, baseline serum 25(OH)D level predicted change in both medial and lateral tibial cartilage volume (β = +0.04% per annum per nmole/liter for both; P < 0.05), and change in serum 25(OH)D level was positively associated with change in medial tibial cartilage volume. These associations were consistent in subjects with radiographic OA and knee pain and/or in women, but not in men or in subjects without radiographic OA or knee pain.

Conclusion

Sunlight exposure and serum 25(OH)D levels are both associated with decreased knee cartilage loss (assessed by radiograph or MRI). This is best observed using the whole range of 25(OH)D levels rather than predefined cut points and implies that achieving vitamin D sufficiency may prevent and/or retard cartilage loss in knee OA.