High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency

ObjectivesRecent large trials indicate that adherence associated with a daily regimen of vitamin D is low and limits anti-fracture efficacy with vitamin D supplementation. The aim of this report is to describe changes of 25-hydroxyvitamin D (25(OH)D) serum concentrations achieved with a single oral dose of 300 000 IU vitamin D3.MethodsOver a course of 4 months, we identified 33 elderly with severe vitamin D deficiency (25(OH)D < 25 nmol/l) on admission to acute care. Patients were admitted for musculoskeletal pain, bone disease, or gait abnormalities. The mean age was 80.5 years (SD ± 6.1). All patients were treated with a single oral dose of 300 000 IU D3 in combination with 500–1000 mg calcium supplements per day depending on their dietary calcium intake.ResultsBaseline mean 25(OH)D serum concentrations were 15 nmol/l (SD ± 5.5). Mean 25(OH)D serum concentrations increased to 81.4 nmol/l (SD ± 29.7) at 3 months (29 patients) and were still 69.0 nmol/l (SD ± 17.9) at 6 months (26 patients). Mean serum calcium levels were 2.24 mmol/l (SD ± 0.11) at baseline, 2.28 mmol/l (SD ± 0.18) at 3 months, and 2.28 mmol/l (SD ± 0.13) at 6 months. Two patients with mild hypercalcemia (2.69 mmol/l) at 3 months had normal values at 6 months.ConclusionBased on our observations, a single oral dose of 300 000 IU vitamin D3 raises mean 25(OH)D serum concentrations to the target mean of above 75 nmol/l at 3 months and a mean level of 69 nmol/l at 6 months. As calcium absorption is enhanced with higher 25(OH)D serum concentrations, calcium supplementation may need downward adjustment with this regimen to avoid mild hypercalcemia.     

Vitamin D inadequacy in French osteoporotic and osteopenic women

ObjectiveStudies have shown that low serum vitamin D levels are associated with secondary hyperparathyroidism, which decreases bone strength and increases fracture risk, most notably after 50 years of age. The objective of this study was to evaluate the vitamin D status of postmenopausal women in France.MethodsWe conducted a cross-sectional observational study of 1292 menopausal women with osteoporosis or osteopenia. The age range was 52–94 years. Serum 25-OH-vitamin D was assayed in each patient. Based on data in the literature, we used four 25-OH-D cutoffs to define vitamin D deficiency: 30, 50, 75, and 80 nmol/L (<12, <20, <30, and <32 ng/ml).ResultsMean serum 25-OH-D was 51.5 ± 26.1 nmol/L (about 20.6 ± 10.4 ng/ml). In the 343 (26.5%) patients taking supplemental vitamin D with or without supplemental calcium, the mean serum 25-OH-D level was significantly higher than in the other patients (65.0 ± 26.0 ng/ml vs. 46.6 ± 18.6 ng/ml; P < 0.001). In the subgroup not taking vitamin D supplements, the prevalence of vitamin D deficiency was 27.3%, 54.1%, 89.9%, and 93.2% with the 30, 50, 75, and 80 nmol/L cutoffs, respectively. The mean 25-OH-D level varied across seasons (P < 0.001), with the highest value being obtained in summer (53.4 ± 18.7 nmol/L; about 21.3 ± 7.5 ng/ml).ConclusionVitamin D deficiency is common among postmenopausal women with osteoporosis or osteopenia in France.     

Low Bone Mineral Density in Rotating-Shift Workers

Shift workers have been reported to have an increased bone resorption. However, no existing evidence indicates lower bone mineral density (BMD) in this group. The objective of this study was to test the hypothesis that a rotating-shift work schedule is associated with low BMD and osteoporosis. We evaluated 70 postmenopausal nurses from the Naval Hospital in Concepcion, Chile. The participants were categorized according to the type of work schedule: 39 had a rotating shift and 31 were daytime workers. Medical history, a health examination, a questionnaire on health-related behaviors and biochemical determinations, and BMD examination were obtained for all participants. When comparing the 2 groups, the rotating-shift workers had lower BMD in the lumbar spine (L1–L4: 0.957 ± 0.15 vs 1.104 ± 0.13; p < 0.05) and lower bone density in both femoral neck bones (right: 0.936 ± 0.17 vs 1.06 ± 0.12; p < 0.05 and left: 0.956 ± 0.19 vs 1.05 ± 0.12; p < 0.05). Additionally, the T-scores for 10 (25.6%) of the rotating-shift workers indicated osteoporosis at lumbar spine (T-score > ?2.5). No evidence of osteoporosis was found for daytime workers. When comparing the 2 groups, the rotating-shift workers had a higher prevalence of osteopenia (T-score = ?1.0 to ?2.5) than the daytime workers: 46.2% vs 35.5%, respectively. We found significant evidence that rotating-shift workers have lower BMD in the trabecular and cortical bones, thus suggesting that this type of work may be a risk factor for osteoporosis. Because this is the first time that this osteoporosis risk factor has been reported, the association needs to be replicated and confirmed in other settings.     

25 hydroxyvitamin D serum levels influence adequate response to bisphosphonate treatment in postmenopausal osteoporosis

It remains unclear whether vitamin D sufficiency optimizes response to bisphosphonate (BP) treatment in postmenopausal osteoporosis. We evaluated the role and possible mechanisms of vitamin D in adequate response to standard BP treatment for postmenopausal osteoporosis.MethodsWe included 120 postmenopausal osteoporotic women (aged 68 ± 8 years) receiving BP (alendronate or risedronate) at their annual follow-up, performing complete anamnesis, including treatment adherence, use of vitamin D supplements, and previous falls and fractures during the last year. We analyzed the evolution of bone mineral density (BMD) during this period and serum PTH and 25 hydroxyvitamin D (25(OH)D) and urinary NTx levels. Patients were classified as inadequate responders to antiosteoporotic treatment based on BMD loss > 2% and/or the presence of fragility fractures during the last year.ResultsThirty percent of patients showed inadequate response to BP treatment, with significantly lower levels of 25(OH)D (22.4 ± 1.3 vs. 26.6 ± 0.3 ng/ml, p = 0.01), a higher frequency of 25(OH)D levels < 30 ng/ml (91% vs. 69%, p = 0.019) and higher urinary NTx values (42.2 ± 3.9 vs. 30.9 ± 2.3 nM/mM, p = 0.01). Patients with 25(OH)D > 30 ng/ml had a greater significant increase in lumbar BMD than women with values < 30 ng/ml (3.6% vs. 0.8%, p < 0.05). The probability of inadequate response was 4-fold higher in patients with 25(OH)D < 30 (OR, 4.42; 95% CI, 1.22–15.97, p = 0.02).ConclusionsInadequate response to BP treatment is frequent in postmenopausal women with osteoporosis as is vitamin D insufficiency, despite vitamin D supplementation. Maintenance of 25(OH)D levels > 30 ng/ml is especially indicated for adequate response to BP treatment.     

Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: A 12-month randomized,clinical trial

PurposeTo examine the effects of 12 mo of resistance training (RT, 2 ×/wk, N = 19) or jump training (JUMP, 3 ×/wk, N = 19) on bone mineral density (BMD) and bone turnover markers (BTM) in physically active (≥ 4 h/wk) men (mean age: 44 ± 2 y; median: 44 y) with osteopenia of the hip or spine.MethodsParticipants rated pain and fatigue following each RT or JUMP session. All participants received supplemental calcium (1200 mg/d) and vitamin D (10 μg/d). BMD was measured at 0, 6, and 12 mo using DXA scans of the whole body (WB), total hip (TH) and lumbar spine (LS). BTM and 25 OHD were measured by ELISA. The effects of RT or JUMP on BMD and BTM were evaluated using 3x2 repeated measures ANOVA (time, group). This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Missouri IRB.ResultsAt baseline, 36 of 38 participants were vitamin D sufficient (25OHD > 50 nmol/L); at 12 mo, all participants were 25OHD sufficient. 25OHD did not differ between groups. WB and LS BMD significantly increased after 6 months of RT or JUMP and this increase was maintained at 12 mo; TH BMD increased only in RT. Osteocalcin increased significantly after 12 mo of RT or JUMP; CTx decreased significantly after 6 mo and returned to baseline concentrations at 12 mo in both RT and JUMP. Pain and fatigue ratings after RT or JUMP sessions were very low at 0, 6, and 12 mo.ConclusionRT or JUMP, which appeared safe and feasible, increased BMD of the whole body and lumbar spine, while RT also increased hip BMD, in moderately active, osteopenic men.     

Functional hypoparathyroidism in postmenopausal women with fragility fracture

IntroductionSecondary hyperparathyroidism sometimes is lacking despite authentic vitamin D insufficiency (VDI) and the concept of functional hypoparathyroidism with a protective role on bone status has been proposed. Therefore, we tested the hypothesis that its prevalence was very low in a population of women with a peripheral fragility fracture.MethodsWe conducted our study in postmenopausal women, admitted for such a fracture in our Fracture Liaison Service. All had bone mineral density (BMD), biochemical assessment and a medical visit.ResultsTwo hundred and thirty seven women (72.9 ± 11.6-year-old) were included and 90.4% had VDI (25[OH]D ≤ 30 ng/mL). Yet, 87.9% of the latter had normal PTH levels less or equal to 64 ng/L. In this population with VDI (n = 214), we found no PTH plateau level related to 25(OH)D. Since a recent study reported an increase in the risk of fracture only when 25(OH)D was below 15 ng/mL, we then used this value as a new threshold. We observed a significant difference in hip BMD between patients with 25(OH)D either less or equal to or greater than 15 ng/mL. However, 81.2% of the formers were still with normal PTH with no difference in BMD whether PTH level was above or within normal range.ConclusionIn a population of postmenopausal women with a fragility fracture, we found that 25(OH)D less or equal to 15 ng/mL was associated with significantly lower hip BMD. Even using this low threshold, we found a high prevalence of functional hypoparathyroidism and it was not associated with any difference in hip or spine BMD. Overall, our results do not support the hypothesis of a protective effect of this biological profile.     

Quantification of Bone Density of the Proximal Femur After Hip Resurfacing Arthroplasty—Comparison of Different DXA Acquisition Modes

Total hip arthroplasty (THA) is a traditional operative procedure in the treatment of osteoarthritis. The hip resurfacing arthroplasty (HRA) provides an alternative to the THA for young active patients. HRA is a bone-preserving procedure eliminating the problem of proximal femoral stress shielding and osteolysis associated to THA. Unfortunately, there is no standardized methodology to monitor the quality of bone after HRA. In this study, areal bone mineral density (BMD) in the operated hip (10 regions of interests [ROIs] of 34 volunteered HRA patients) was measured using Lunar Prodigy dual-energy X-ray absorptiometry, and the agreement of a standard (dual femur) and an orthopedic (orthopedic hip) acquisition modes was compared. Furthermore, reproducibility of the patient-specific analysis procedures was tested. The analysis procedures were reproducible with both acquisition modes (1.18%–1.37%). The mean (±standard deviation) difference between the acquisition modes was 1.46 ± 0.93%. At ROIs, a strong linear relationship was found between the results from 2 acquisition modes (R² = 0.801–0.966, p < 0.01). In conclusion, both acquisition modes were reproducible, and it is suggested that the error induced by the different acquisition modes does not affect interpretation of BMD changes after HRA surgery.     

Navel Jewelry Artifacts and Intravertebral Variation in Spine Bone Densitometry in Adolescents and Young Women

Non-removable navel jewelry can increase the measured bone density of the underlying vertebra. We measured lumbar spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) in an observational study of 727 adolescents and young women aged 14–30 yr. We evaluated several methods of correcting BMD: manually erasing a small area, eliminating 1 or 2 vertebrae, estimating the BMD from 1 or 2 vertebrae using data from remaining vertebrae, and estimating the BMD using T-scores of the remaining vertebrae. Ten percent (n = 71) of the subjects were wearing navel jewelry. The areal BMD by DXA of L1 and L2 was similar in those with jewels as in controls without jewels, but L3–L4 showed higher bone density in those with jewelry, and the spine BMD of L1–L4 was significantly higher in the bejeweled women (1.043 ± 0.011 vs 1.006 ± 0.004 g/cm², p = 0.01). The estimated errors in accuracy (g/cm²) were 0.034 due to the jewels; 0.005 from erasing a small area; 0.019 from eliminating L4; 0.044 from eliminating both L3 and L4; 0.016 from predicting BMD using L1–L3; and 0.028 using L1–L2. The T-scores using the Hologic database were progressively lower in the caudal vertebrae, even in 96 local women aged 30–35 yr, whose average T-score was 0.35 at L1 but ?0.26 at L4. Thus, we found significant errors due to intravertebral variability. We suggest the optimal method of correcting for small artifacts is to erase the area under the artifact.     

Bone Mineral Density in Premenopausal Arab Women With Type 2 Diabetes Mellitus

IntroductionThis study compares an ethnically uniform group of premenopausal type 2 diabetic (T2DM) Arab women with a matched control group of nondiabetic subjects, in terms of their bone mineral density (BMD) and anthropometric measurements.MethodsThe study included 252 premenopausal Arab women. Their age ranged from 26 to 50 yr with a mean ± SD of 43.65 ± 8.97 yr. One hundred and twenty-two women were T2DM patients and 130 women were nondiabetic controls. The controls matched the subjects in gender, age, and body mass index (BMI). BMD was measured at total lumbar spine (L1–L4) and total left hip, using dual-energy X-ray absorptiometry (DXA; HOLOGIC, QRS SERIES, Europe, Belgium). Difference in BMD and its relationship to the anthropometric measurements in T2DM and control groups were assessed.ResultsSignificant difference was found between T2DM patients and nondiabetic patients in their mean hip BMD (0.92 ± 0.16 vs. 0.87 ± 0.14, p < 0.05) and spine BMD (0.93 ± 0.15 vs. 0.88 ± 0.14, p < 0.01). No significant difference was found in age, height, weight, and BMI (p > 0.05). The increase in hip BMD in T2DM patients normalized and the increase in spine BMD persisted after controlling for the confounding effect of age and anthropometric measurements.ConclusionPremenopausal Arab women with T2DM have higher BMD at the spine than women without T2DM. The underlying mechanism causing this increase does not seem to be related to ethnicity, gender, hormonal status, or anthropometric measurements.     

Maternal Vitamin D Status During Pregnancy and Bone Mass in Offspring at 20 Years of Age: A Prospective Cohort Study

It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results; none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study. Maternal serum samples collected at 18 weeks gestation were assayed for 25‐hydroxyvitamin D (25OHD). Outcomes were total body bone mineral content (BMC) and bone mineral density (BMD) measured by dual‐energy X‐ray absorptiometry in offspring at 20 years of age. The mean (± SD) maternal serum 25OHD concentration was 57.2 ± 19.2 nmol/L; 132 women (38.7%) were vitamin D‐deficient (25OHD <50 nmol/L). After adjustment for season of sample collection, maternal factors, and offspring factors (sex, birth weight, and age, height, lean mass, and fat mass at 20 years), maternal 25OHD concentration was positively associated with total body BMC and BMD in offspring, with a mean difference of 19.2 (95% confidence interval [CI], 5.6–32.7) g for BMC and 4.6 (95% CI, 0.1–9.1) mg/cm² for BMD per 10.0 nmol/L of maternal 25OHD. Maternal vitamin D deficiency was associated with 2.7% lower total body BMC (mean ± SE) (2846 ± 20 versus 2924 ± 16 g, p = 0.004) and 1.7% lower total body BMD (1053 ± 7 versus 1071 ± 5 mg/cm², p = 0.043) in the offspring. We conclude that vitamin D deficiency in pregnant women is associated with lower peak bone mass in their children. This may increase fracture risk in the offspring in later life. © 2014 American Society for Bone and Mineral Research.     

Bone mineral density and importance of strict gluten-free diet in children and adolescents with celiac disease

ObjectivesLow bone mineral density (BMD) is common in children and adolescents with celiac disease. Strict gluten-free diet (GFD) improves bone mineralization, even in 1 year. The effect of occasional gluten intake is not known. The aims of this study were to compare BMD and prevalence of low BMD in children and adolescents on strict and not strict GFD.MethodsWe measured BMD in 55 children and adolescents (strict GFD) with negative endomysium antibodies (EMA) in the last 2 years and in 19 (not strict GFD) with positive EMA at the time of the study. Lumbar, left hip and total body BMD were measured by dual-energy X-ray absorptiometry. Four-day weighted dietary protocols were obtained by means of a self-completed questionnaire of total food and beverage intake. Energy and calcium intake were calculated using nutrition data software. EMA, tissue transglutaminase antibodies, serum calcium, phosphate, 25-hydroxy vitamin D, intact parathormone, albumin, urea and creatinine levels were determined in all patients.ResultsBMD in patients on strict GFD was significantly higher than in patients on not strict GFD (lumbar p = 0.01; total body p = 0.005). There were significantly more patients with total body BMD below ? 1.0 in not strictly compliant group (71% compared to 38%; p = 0.03). Calcium intake and vitamin D levels were below recommendations in both groups.ConclusionChildren and adolescents on not strict GFD are at increased risk for low BMD. We therefore recommend that BMD should be evaluated in patients with positive EMA. In addition, patients on strict GFD are at risk for low BMD because of low calcium intake or vitamin D deficiency. Therefore, strict GFD with recommended calcium intake and vitamin D supplementation during winter and spring should be encouraged in all children and adolescents with celiac disease.     

Effect of beta-blockers on bone mass and biomechanical parameters of the femoral neck in males with acute myocardial infarction

ObjectivesEvaluate the effect of cardioselective β-blockers on bone mass and biomechanical properties of the femoral neck in males with acute myocardial infarction.MethodsForty males with acute myocardial infarction were studied during one year. Seventy-five percent of the patients (30 patients) were treated with cardioselective β-blockers and 10 were not similarly treated. A hip densitometry was performed upon release and one year later. The BMD was measured in the femoral neck and in biomechanical elements obtained by DXA.ResultsBoth groups had similar clinical conditions at the beginning of the study and after a one-year follow-up. No differences in the BMD (0.934 ± 0.12 vs. 0.921 ± 0.14) were observed in the group without β-blockers or in the group with β-blockers (0.980 ± 0.12 vs. 0.977 ± 0.12). No differences were observed in the measured structural parameters.ConclusionThe cardioselective β-blockers do not modify bone mass or the structural bone parameters in males with acute myocardial infarction.     

Mild to moderate cognitive impairment is a major risk factor for mortality and nursing home admission in the first year after hip fracture

BackgroundIt is not well established if and to what extent mild to moderate cognitive impairment predicts mortality and risk of nursing home admission after hip fracture.ObjectiveTo investigate prospectively whether and to what extent mild to moderate cognitive impairment, contributes to mortality and admission to nursing home in the first year after acute hip fracture.MethodsWe enrolled 173 patients with acute hip fracture age 65 and older who reached a Mini-Mental State Examination (MMSE) score of at least 15 during acute care after hip fracture repair. An MMSE score of 15 to 24 (median) was classified as mild to moderate cognitive impairment. Primary outcomes were mortality in all and admission to nursing home among seniors who lived at home prior to their hip fracture. Follow-up was 12 months with clinical visits at baseline, 6, and 12 months, plus monthly phone calls. We used Cox proportional hazards models controlling for age, sex, body mass index, baseline number of comorbidities and 25-hydroxyvitamin D status, and severe incident infections to assess the risk of mortality and nursing home admission. Because the study population was enrolled in a factorial design clinical trial testing high dose vitamin D and/or an exercise home program, all analyses also controlled for these treatment strategies.ResultsOf 173 acute hip fracture patients enrolled, 79% were women, 77% were admitted from home, and 80% were vitamin D deficient (< 20 ng/ml). Mean age was 84 years. 54% had mild to moderate cognitive impairment. Over the 12-month follow-up, 20 patients died (27% of 173) and 47 (35% of 134) were newly admitted to a nursing home. Mild to moderate cognitive impairment was associated with a more than 5-fold increased risk of mortality (HR = 5.77; 95% CI: 1.55–21.55) and a more than 7-fold increased risk of nursing home admission (HR = 7.37; 95% CI: 1.75–30.95). Additional independent risk factors of mortality were male gender (HR = 3.55; 95% CI: 1.26–9.97), low BMI (HR = 7.25; 95% CI: 1.61–33.74), and baseline 25-hydroxyvitamin D level (per 1 ng/ml: HR = 0.93; 95% CI: 0.87–0.998; p = 0.04).ConclusionsMild to moderate cognitive impairment in patients with acute hip fracture is associated with a high risk of mortality and nursing home admission during the first year after hip fracture. Female gender, a greater BMI and a higher 25-hydroxyvitamin D status may protect against mortality after hip fracture independent of cognitive function.     

Underestimated Fracture Probability in Patients With Unilateral Hip Osteoarthritis as Calculated by FRAX

Osteoporosis (OP) and osteoarthritis (OA) are age-related diseases often considered to be mutually exclusive. We previously found that 25% of women with advanced OA had occult OP and that femoral neck (FN) bone mineral density (BMD) T-scores were significantly higher for osteoarthritic vs contralateral hips. The FRAX calculator incorporates clinical risk factors and FN BMD T-score to estimate 10-yr total fracture probability and hip fracture probability. In 35 women and men aged 41 yr or older with unilateral hip OA scheduled for hip replacement, we tested whether FRAX fracture probability is underestimated when using data for the OA rather than the contralateral hip. There were between-hip differences for FN BMD T-score (p < 0.0001), total fracture probability (p = 0.0004), and hip fracture probability (p = 0.0009). Use of FN BMD T-scores resulted in OP treatment recommendations for 0% and 11% of subjects compared with 11% and 17% for total fracture probability and hip fracture probability, respectively. In 6–11% of subjects in this series, the FRAX calculator underestimated fracture probability with data for the OA hip. With the increased use of FRAX in clinical use, these data suggest that measurement of BMD at the contralateral hip may yield higher calculated FRAX total and hip fracture probabilities.     

Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis

IntroductionBreast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.MethodsThe effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.ResultsIn vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)₂D₃ inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49 ± 0.08 mm² versus 1.68 ± 0.15 mm², P < 0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81 ± 0.13 mm² versus 0.52 ± 0.11 mm² in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.ConclusionVitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.     

Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice

IntroductionPreviously, little attention has been paid as to how disturbances in the parathyroid hormone (PTH)–calcium–vitamin D-axis, such as secondary hyperparathyroidism (SHPT), relate to mortality amongst hip fracture patients. This study aimed to (1) determine if SHPT is associated with mortality in this group of patients, (2) investigate the association between serum (s-) PTH, s-total calcium, s-25-hydroxyvitamin D (s-25(OH)D) and mortality and (3) determine the prevalence of SHPT amongst hip fracture patients and a control group.MethodThe study included 562 hip fracture patients (HF) (age ≥ 70 years) admitted to a Danish university hospital. The hip fracture patients were prospectively enrolled in a dedicated hip fracture database. Each hip fracture patient was exactly matched according to age and sex with two controls randomly chosen from a control population of 21,778 subjects who had s-PTH, s-total calcium and s-25(OH)D measured at the Copenhagen General Practitioners Laboratory after referral from their general practitioner. The control group (Con) thus consisted of 1124 subjects.ResultsGeneral 1-year mortality: Con-female 8.4%, Con-male 15.3%, HF-female 24.6%, HF-male 33.3%, p < 0.0001 (log rank).SHPT and related 1-year mortalityCon-no SHPT 8.9%, Con-SHPT 16.8%, HF-no SHPT 22.7%, HF-SHPT 34.9%, p < 0.0001 (log rank). The mortality rates were higher for controls with SHPT (OR 2.06, 95% CI: 1.32–3.23), hip fracture patients without SHPT (OR 3.00, 95% CI: 2.14–4.20) and hip fracture patients with SHPT (OR 5.46, 95% CI: 3.32–8.97) compared to the controls without SHPT.Prevalence of SHPTCon 16%, HF 20%, p = 0.09 (Chi-square).ConclusionsOur study clearly shows that SHPT is significantly associated with mortality in both hip fracture patients and the control group. In the multivariate Cox regression analysis, s-PTH and s-total calcium were both significantly associated with mortality, whereas s-25(OH)D was not associated with mortality in this analysis. Our study furthermore indicates that SHPT is almost equally prevalent amongst the hip fracture patients and the control group.     

Single high-dose oral vitamin D3 (stoss) therapy — A solution to vitamin D deficiency in children with cystic fibrosis?

ObjectivesTo determine the safety and efficacy of stoss therapy on vitamin D levels over a 12 month period in children with cystic fibrosis and vitamin D deficiency (< 75 nmol/L).Study designRetrospective chart review of 142 paediatric CF patients from 2007 till 2011.ResultsThirty eight children received stoss therapy and 37 children with vitamin D deficiency were not treated and served as a control group. The stoss treated group had a significant and sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12 months post treatment compared to controls (94.82 ± 41.0 nmol/L, p = 0.001; 81.54 ± 24.6 nmol/L, p = 0.001; 92.18 ± 36.5 nmol/L, p = 0.008 and 64.6 ± 20.0 nmol/L, p = 0.006 respectively). At 12 months post intervention, the mean difference in vitamin D levels from baseline between the stoss treated group and controls was significant at 15 nmol/L compared to 5 nmol/L (p = 0.038).ConclusionStoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D greater than 75 nmol/L over 12 months.     

Bone Mineral Density Measured by a Portable X-ray Device Agrees With Dual-Energy X-ray Absorptiometry at Forearm in Preschool Aged Children

Dual-energy X-ray absorptiometry (DXA) measures of bone mineral density (BMD) are generally not feasible in fieldwork. The present study determined the agreement between BMD measured by DXA and portable peripheral DXA in preschool aged children. Fifty-seven children (4.2 ± 1.0 yr) had their nondominant distal forearm scanned using a peripheral DXA scanner (PIXI; GE Medical Systems Lunar, Madison, WI) at their daycare and a DXA (4500A Discovery Series; Hologic Inc., Bedford, MA) at our research clinic. Correlation analysis, one-way analysis of variance, and Bland-Altman plots were performed to examine the agreement between measurements. Data were also divided into tertiles for cross-classification analysis and calculation of kappa coefficients. Distal forearm BMD measured by PIXI was significantly correlated with DXA measures of total forearm BMD (r > 0.51; p < 0.001), proximal 1/3 BMD (r > 0.41; p < 0.001), mid-BMD (r > 0.37; p < 0.001), and ultradistal (UD) BMD (r > 0.57; p < 0.001). Cross-classification in the same or adjacent tertile between measures (UD forearm: 96.5%; UD radius: 94.4%; total forearm: 87.7%; total radius: 84.2%) resulted in weighted kappa coefficients of 0.46, 0.58, 0.42, and 0.43, respectively. Bland-Altman plots further clarified these agreements as all had low bias (UD forearm: bias = 0.003 ± 0.002; UD radius: ?0.015 ± 0.021; total forearm: ?0.062 ± 0.027; total radius: ?0.077 ± 0.026). These results demonstrate that portable DXA measures of forearm BMD agree moderately with DXA.     

Vitamin D levels in 577 consecutive elective foot & ankle surgery patients

BackgroundVitamin D deficiency is a global concern impacting upon large communities and certain disease populations. It can adversely affect the outcome of orthopaedic operations. We aimed to perform an audit of the Vitamin D status of patients in two centres in the United Kingdom undergoing elective foot and ankle surgery.MethodsSerum 25-hydroxyvitamin-D (vitamin D) levels were obtained prospectively in 577 consecutive elective patients undergoing elective foot and ankle surgery between October 2014 and March 2017 (29 months). Variables including age, gender, ethnicity, location, season, month and procedure type were recorded.Results577 patients were included over the study period. 62.0% were female. Mean age was 53.2 (median 54.5, range 16.7–86.6). 300 patients were treated in Northampton and 277 in Leicester. The serum 25-hydroxyvitamin-D levels for the patient group were normally distributed. The mean was 52.3 nmol/L (SD 28.0; range 7.5–175) and the median 47.5 nmol/L. 21.7% were grossly deficient, 31.9% deficient, 28.9% insufficient and 17.5% within normal range. Age, gender and procedure type did not statistically affect vitamin D levels (p = 0.5, t-test). Ethnicity, location and Winter season did affect Vitamin D levels (p < 0.05). August was the most significant month with levels significantly higher than January, February, March, April, June, November and December (p < 0.05, one-way ANOVA).ConclusionsOnly 1 in 5.7 patients had a normal Vitamin D level and 1 in 4.6 were grossly deficient. Ethnicity and patient location significantly affected Vitamin D results. Summer months were noted to demonstrate significantly the highest levels and August the highest. We did not find that age or gender affected Vitamin D levels in our cohort.