Impact of vitamin D-related serum PTH reference values on the diagnosis of mild primary hyperparathyroidism, using bivariate calcium/PTH reference regions

Background, objective An international consensus conference underlined the importance of defining upper parathyroid hormone (PTH) reference values based on 25‐OH‐vitamin D [25(OH)D] to diagnose mild primary hyperparathyroidism. We determined the importance of this factor in a Belgian population. Design, patients, methods Intact PTH and 25(OH)D were measured in 261 healthy controls (18–65 years, winter/summer). They were classified as 25(OH)D replete (50–153 nmol/l; n = 129) or deplete (8–50 nmol/l; n = 132). PTH was determined in 49 patients with surgically proven primary hyperparathyroidism. PTH thresholds for 95% specificities and corresponding sensitivities were computed from both 25(OH)D replete and deplete receiver operating characteristic (ROC) curves. The 95% bivariate reference ellipses, relating PTH to calcium for 25(OH)D replete and deplete controls, were compared to the PTH/calcium pairs of patients with primary hyperparathyroidism. Results Parathyroid hormone correlated with 25(OH)D (r = ?0·3232; P < 0·0001). PTH normative values were 20% lower in 25(OH)D replete than deplete controls (P < 0·0001). PTH thresholds, providing 95% specificities for primary hyperparathyroidism diagnosis, were 7·6 pmol/l and 5·8 pmol/l, using ROC curves derived from 25(OH)D deplete or replete controls, respectively. Corresponding sensitivities were of 56%vs 88%, respectively (P < 0·05). The 95% PTH/calcium bivariate reference ellipses for?deplete and replete 25(OH)D controls differed, but the PTH/calcium pairs of patients with primary hyperparathyroidism did not overlap these ellipses. Conclusion For a given specificity, primary hyperparathyroidism diagnostic parathyroid hormone thresholds were lower and sensitivities higher using ROC curves, derived from 25(OH)D replete vs deplete controls. The 25(OH)D status does not affect the efficiency of primary hyperparathyroidism diagnosis, using bivariate PTH/calcium reference density ellipses.     

Relationships with serum parathyroid hormone in old institutionalized subjects

OBJECTIVE AND BACKGROUND: Old people in residential care are at the highest risk of any group for hip fracture. This may relate to their high prevalence of hyperparathyroidism. There are few data, however, on relationships with serum parathyroid hormone (PTH) in these individuals. This study therefore examined complex associations with serum PTH in nursing home and hostel residents. DESIGN: Cross-sectional analysis. PATIENTS: One hundred and forty-three nursing home and hostel residents of median age 84 years. MEASUREMENTS: Serum PTH, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D), plasma creatinine, phosphate, calcium, albumin, Bsm-1 vitamin D receptor genotype, age, weight and use of frusemide or thiazide. RESULTS: The statistical models determined accounted for half the interindividual variation in serum PTH. Heavier weight was associated with both the prevalence of secondary hyperparathyroidism and the serum concentration of PTH. Novel interactions with serum PTH were identified between: weight and 25OHD; 25OHD and phosphate; and phosphate and thiazide diuretic use. Plasma phosphate was associated with PTH independently of calcium and 1,25-(OH)2D. There was no independent association between PTH and nuclear vitamin D receptor genotype. CONCLUSIONS: Heavier weight is associated with both the prevalence and severity of secondary hyperparathyroidism and consistent with animal models of secondary hyperparathyroidism, phosphate may relate to serum PTH independently of 1,25-(OH)2D or calcium.     

Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality

Objective To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality. Design A prospective cohort study. Patients A total of 1280 older men and women living in residential care facilities. Measurements We measured baseline serum 25‐hydroxyvitamin D (25OHD), serum intact PTH, serum amino‐terminal propeptide of type I collagen (PINP) and serum carboxy‐terminal telopeptide of type I collagen (CTX‐I). Deaths and fractures were recorded prospectively. Results Hypovitaminosis D (25OHD < 39 nmol/l) and absence of secondary hyperparathyroidism (PTH > 7·0 pmol/l) in the presence of hypovitaminosis D were common in this sample with a prevalence of 77·5% and 53·3%, respectively. In the presence of hypovitaminosis D, residents showing a hyperparathyroid response (n = 406) had significantly higher serum bone turnover markers than individuals with serum PTH levels ≤ 7·0 pmol/l (termed ‘low vitamin D, normal PTH’, n = 463). After adjusting for risk factors, mortality was significantly higher in the secondary hyperparathyroidism group than in the ‘low vitamin D, normal PTH’ group [hazard ratio (HR) = 1·35, 95% confidence interval (CI) 1·12–1·64; P = 0·002]. All residents with serum PTH levels ≤ 7·0 pmol/l (n = 603) were similar with regard to both bone turnover and mortality, independent of their actual vitamin D status. Conclusion Absence of secondary hyperparathyroidism in the presence of hypovitaminosis D appears to be common in the frail elderly and is associated with longer survival, similar to that observed in vitamin D‐replete elderly subjects.     

Calcium metabolism in the frail elderly

Elderly residents of aged care facilities are usually considered at high risk of osteoporosis not only due to their age, but also due to nutritional factors, poor sunlight exposure and renal insufficiency. This study aimed to describe calcium metabolism and related hormones in this high-risk population. A total of 1280 elderly residents of hostels and nursing homes in the northern Sydney area (aged 65 years or over) had serum analysis for clinical chemistry including serum 25-hydroxy vitamin D (25OHD) and parathyroid hormone (PTH). Moderate renal impairment (creatinine clearance 30–60 ml/min) was common (62%), but hypocalcaemia was uncommon (7.0%). Mild hypoalbuminaemia was common (34% below 40 g/l, but only 3.2% below 35 g/l); 77.5% of the cohort had low serum 25OHD levels (<39 nmol/l) and 41.7% had elevated PTH levels (>66 pg/ml). Independent predictors of low serum 25OHD levels included gender, age, serum PTH, season, mobility and creatinine clearance. Use of vitamin D supplementation conferred modestly higher serum 25OHD levels (45.5 vs 27.1 nmol/l in non-supplemented residents, p<0.0001) and lower PTH levels (50.0 vs 78.1 pg/ml, p<0.0001). Despite adequate overall nutrition, vitamin D deficiency is present in the majority of this population. Vitamin D deficiency remains a significant public health problem in the institutionalized frail elderly. Currently available supplements are not adequate or utilized frequently enough to address this problem.     

The relationship between PTH and 25-hydroxy vitamin D early in pregnancy

Objective Measure serum PTH and 25(OH)D in a cross‐sectional sample of pregnant women at 11th through 13th weeks’ gestation to examine vitamin D status and consider implications. Design Observational: we retrieved residual sera stored at ?20 °C after routine first trimester Down’s syndrome screening, distributed over 12 months. Patients 430 African American women and 586 Caucasian women. Measurements PTH and 25‐hydroxy vitamin D [25(OH)D] immunoassays. Results PTH medians were: 1·33 pmol/l (African American women); 1·20 pmol/l (Caucasian women) (t = 0·43, P = 0·7). Concentrations were highest in winter and decreased significantly in spring, fall, and summer. There was a direct PTH/weight relationship in Caucasian (t = 3·12, P < 0·002), but not African American women (t = 1·34, P = 0·18). Median 25(OH)D concentrations were 47·5 nmol/l (African American women) and 65 nmol/l (Caucasian women) (t = 13·7, P < 0·001). Concentrations were lowest in winter and rose significantly in spring, fall, and summer. Reciprocal 25(OH)D/weight relationships existed for both racial groups (t = ?4·31 P < 0·001; t = 4·54, P < 0·001, respectively). Among 68 Caucasian women who smoked, median PTH and 25(OH)D concentrations were somewhat lower (P = ns). In separate regression models with PTH and 25(OH)D [dependent variables] and season, weight and smoking [independent variables], the only qualifying interactive term was in the Caucasian PTH model (season*1/weight). A regression model applied to adjusted scatter plots of PTH vs 25(OH)D indicated a weak relationship. Conclusions The PTH/25(OH)D relationship is weaker during early pregnancy than in non‐pregnant adults, making it unreliable for estimating vitamin D sufficiency. A suitable reference point for sufficiency might be the maternal 25(OH)D level considered sufficient for adequate transfer to neonates.     

Vitamin D insufficiency prior to bariatric surgery: risk factors and a pilot treatment study

Objective To assess vitamin D status and the influences of race, sun exposure and dietary vitamin D intake on vitamin D levels, and to evaluate two vitamin D repletion regimens in extremely obese patients awaiting bariatric surgery. Methods A cross‐sectional analysis of dietary vitamin D, sun exposure, PTH [intact (iPTH) and PTH(1‐84)] and 25‐hydroxyvitamin D (25OHD; differentiated 25OHD2 and 25OHD3) in 56 obese [body mass index (BMI) > 35 kg/m²] men and women (age 20–64 years). In a pilot clinical trial, 27 subjects with 25OHD levels < 62 nmol/l were randomized to receive ergocalciferol or cholecalciferol for 8 weeks. Results Serum 25OHD was low (mean 45 ± 22 nmol/l) and was inversely associated with BMI (r = ?0·36, P < 0·01). Each BMI increase of 1 kg/m² was associated with a 1·3 nmol/l decrease in 25OHD (P < 0·01). BMI, sun exposure, African American race and PTH predicted 40% of the variance in 25OHD (P < 0·0001). Serum 25OHD significantly increased at 4 and 8 weeks in both treatment groups (P < 0·001), whereas PTH(1‐84) declined significantly in subjects treated with cholecalciferol (P < 0·007) and tended to decrease following ergocalciferol (P < 0·09). Conclusions In severely obese individuals, those who are African American, have higher BMI and limited sunlight exposure are at greatest risk for vitamin D insufficiency. These demographic factors can help to identify at‐risk patients who require vitamin D repletion prior to bariatric surgery. Commonly prescribed doses of ergocalciferol and cholecalciferol are effective in raising 25OHD. Further investigation is needed to evaluate whether these regimens have differential effects on PTH, and to determine the optimal regimen for vitamin D repletion in the extremely obese patient.     

Discrepant influence of vitamin D status on parathyroid hormone and bone mass after two years of calcium supplementation

Objective To investigate the influence of vitamin D status on parathyroid hormone and bone mass after a 2‐year supplementation of calcium alone. Patients and Methods Randomized, double‐blind, placebo‐controlled clinical trial, in healthy postmenopausal women without osteoporosis: three hundred and thirty‐six subjects aged 60–97 years were studied and randomized to receive elemental calcium 500 mg/day (n = 175) or placebo (n = 161) for 2 years. Measurements Changes in parathyroid hormone (PTH) and bone mineral density (BMD) from baseline and vitamin D status. Values are presented as means ± SD. Results After 2 years, subjects with calcium supplementation had significant decrease in plasma PTH level (4·4 ± 1·7 vs 4·7 ± 1·9 pmol/l, P < 0·01), improved lumbar BMD (1·031 ± 0·12 vs 1·004 ± 0·12 g/cm², P < 0·001) and total hip BMD (0·890 ± 0·10 vs 0·883 ± 0·10 g/cm², P < 0·001) without change in femoral neck BMD. In the placebo group, PTH level significantly increased (4·8 ± 1·6 vs 4·5 ± 1·5 pmol/l, P < 0·001), lumbar BMD slightly increased (1·027 ± 0·14 vs 1·018 ± 0·14 g/cm², P < 0·001), total hip and femoral neck BMD decreased (0·876 ± 0·11 vs 0·887 ± 0·11 g/cm², P < 0·001 and 0·783 ± 0·10 vs 0·798 ± 0·10 g/cm², P < 0·001, respectively). When subjects were classified according to baseline 25‐hydroxyvitamin D [25(OH)D] levels into those with 25(OH)D in the lower tertile (lowVitD) and those in the middle and upper tertiles combined (normVitD). The degree of PTH suppression after calcium supplementation was significantly higher in the normVitD compared to the lowVitD groups (?5·6 ± 26·7%vs 1·3 ± 27·2%, P < 0·05). No effect of vitamin D status on the change in lumbar BMD after calcium supplementation was demonstrated. Despite the higher suppression of PTH, there was a slight decrease in femoral neck BMD after calcium supplementation in the normVitD group while femoral neck BMD was more or less maintained in the lowVitD group (?0·6 ± 3·2%vs 0·5 ± 2·9%, P < 0·05). Conclusion Calcium supplementation appears to affect femoral bone mass less in Thai postmenopausal women with adequate vitamin D status, despite higher suppression of PTH.     

High parathyroid hormone,but not low vitamin D concentrations,expose elderly inpatients to hypertension

Aim: Serum parathyroid hormone (PTH) and 25‐hydroxyvitamin D (25OHD) concentrations might contribute to blood pressure (BP) levels. Mixed results in previous literature could be due to the failure to consider both these hormones concurrently, despite their long‐known relationship. Our objective was to examine the association of serum intact PTH and 25OHD concentrations with BP levels amongst older inpatients, while accounting for each other. Methods: The participants were 284 Caucasian older inpatients with no suspicion of primary hyperparathyroidism (mean age 85.87 ± 5.90 years; 65.8% female) admitted to the geriatric acute care unit of Angers University Hospital, France. They were divided into two groups according to the existence of hypertension (i.e. systolic blood pressure [SBP] >140 mmHg, or diastolic blood pressure [DBP] >90 mmHg). Age, sex, numbers of chronic diseases and of drugs taken daily, use of antihypertensive or corticosteroid drugs and of calcium supplements/vitamin D, thyroid‐stimulating hormone and albumin concentrations, creatinine clearance, and season tested were used as covariables. Results: Hypertensive participants (n = 106) had higher intact PTH concentrations than normotensive patients (P = 0.044). There was a positive linear association of BP with intact PTH concentrations (adjusted β = 0.08, P = 0.015 for SBP; adjusted β = 0.05, P = 0.044 for DBP), but not with vitamin D. Serum intact PTH concentration, unlike 25OHD, was associated with hypertension (adjusted OR 1.01, P = 0.038). Conclusions: Irrespective of 25OHD, PTH was associated with hypertension by increasing both SBP and DBP. Geriatr Gerontol 2013; 13: 783–791 .     

Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hostel.

OBJECTIVES: To determine whether falling relates to serum levels of vitamin D and parathyroid hormone. DESIGN: A cross-sectional study with retrospective analysis. SETTING: An aged-care institution in Melbourne Australia. PARTICIPANTS: Ambulant nursing home and hostel residents (n = 83). MEASUREMENTS: Frequency of falling, frequency of going outdoors, use of cane or walker, age, sex, weight, type of accommodation, and duration of residence. Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone (PTH). Plasma concentrations of albumin, calcium, phosphate, and creatinine. Use of furosemide or non-benzodiazepine anticonvulsants. RESULTS: Median age of residents was 84 years. The cohort was vitamin D deficient with a median (interquartile range) 25-hydroxyvitamin D level of 27 (18-37) nmol/L (one-third the reference range median), P < .001. The median (interquartile range) PTH of 5.2 (3.8-7.7) pmol/L exceeded the reference range median, P < .001. Residents who fell (n = 33) had lower serum 25-hydroxyvitamin D levels than other residents (medians 22 vs 29 nmol/L, P = .02) and higher serum PTH levels (medians 6.2 vs 4.8 pmol/L, P < .01). Sixty residents lived in the hostel (72%), and 41 (49%) walked without any walking aid. In a multiple logistic regression for falling, higher serum PTH remained independently associated with falling, with an odds ratio (95% confidence interval) for falling of 5.6 (1.7-18.5) per unit of the natural logarithm of serum PTH. Other terms in the regression were hostel accommodation, odds ratio .04 (.01-.25), and ability to walk without aids, odds ratio .07 (.01-.37). CONCLUSIONS: In ambulant nursing home and hostel residents, residents who fall have lower serum 25-hydroxyvitamin D and higher serum parathyroid hormone levels than other residents. The association between falling and serum PTH persists after adjustment for other variables.     

Determinants of plasma PTH and their implication for defining a reference interval

Background To improve the diagnostic sensitivity of PTH measurements, more data on the upper limit of the reference interval for PTH levels were requested at a recent international consensus conference. As PTH levels vary inversely with plasma 25‐hydroxyvitamin D (25OHD) levels and as vitamin D insufficiency is widespread, particular attention should be given to the influence of low vitamin D levels on the PTH reference interval. Aim, design and methods In a cross‐sectional design, including 2316 women aged 17–84, we determined 95% reference interval using a nonparametric approach and studied the effects of potential predictors on plasma PTH levels. Results PTH was a positive function of age, body weight and BMI and inversely associated with total daily calcium intake, smoking, plasma calcium levels and 25OHD levels, all of which explained 16% of the variability in plasma PTH levels. The threshold value for 25OHD levels below which PTH levels started to rise was 82 nmol/l. Plasma PTH levels varied inversely with the seasonal variations in 25OHD levels. Mean PTH level was 4·1 pmol/l with a reference interval equal to 2·0–8·6 pmol/l. Restricting the population in whom the reference interval was calculated to only women with 25OHD levels above 30 or 100 nmol/l lowered the upper limit of the reference interval to 8·4 and 7·1 pmol/l, respectively. Similar, stratification according to age, body mass index, smoking and calcium intake had only minor impact on the reference interval. Conclusion Indices with known effects on plasma PTH levels have only a minor impact on the upper levels of the normative reference interval in women with intact renal function.     

Prophylactic vitamin D in healthy infants: assessing the need

The objective was to evaluate the need for vitamin D prophylaxis in healthy infants. This was a prospective and randomized study performed at primary care clinics. Eighty-eight full-term 1-month-old healthy infants were randomly assigned to receive (n = 41) or not (n = 47) 402 IU/d of vitamin D for 1 year. Primary outcome measures were serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations at 3, 6, and 12 months of age; secondary measures included data on feeding, habitat, season of birth, sun exposure, and physical examination. At 3 and 6 months of age, serum 25OHD levels (±SD) were significantly higher (P < .001) in the prophylaxis group. In the group without prophylaxis, serum 25OHD increased with age; and breast-fed infants aged 3 months had the lowest value (20.2 ± 9.4 ng/mL), which was significantly (P = .001) lower than that of formula-fed infants (35.0 ± 9.7 ng/mL). The PTH levels were not influenced by the prophylaxis or feeding. No influence of either the habitat or season of birth on serum 25OHD concentrations was demonstrated. No infant had clinical signs of vitamin D deficiency. Serum 25OHD and PTH concentrations were weakly but significantly correlated (r = −0.29, P = .009) at 3 months of age. Healthy infants without vitamin D prophylaxis had lower circulating concentrations of 25OHD at 3 and 6 months of age, the lowest value being found in 3-month breast-fed infants. The clinical relevance of these findings is probably negligible because serum 25OHD levels spontaneously increased with age and were not associated with high serum PTH. Clinical manifestations of rickets were not observed.     

A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial

Vitamin D deficiency leads to secondary hyperparathyroidism, increased bone turnover, and bone loss and, when severe, to osteomalacia. Vitamin D deficiency is common in elderly people, especially the institutionalized. The definition of vitamin D deficiency is hampered by the fact that large interlaboratory differences exist in assays for serum 25-hydroxyvitamin D (25OHD), the main circulating metabolite. The international Multiple Outcomes of Raloxifene Evaluation study, a large prospective intervention trial in postmenopausal women with osteoporosis, offered the opportunity to compare vitamin D status and parathyroid function throughout many countries over the world. For this study, baseline data were available from 7564 postmenopausal women from 25 countries on 5 continents. All women had osteoporosis, i.e. bone mineral density (BMD) at femoral neck or lumbar spine was lower than t-score -2.5, or they had 2 vertebral fractures. Serum 25OHD was measured by RIA, and serum PTH was measured by immunoradiometric assay. BMD was measured by dual x-ray absorptiometry. The mean (+/-SD) serum 25OHD was 70.8 +/- 30.9 nmol/L. A low serum 25OHD (<25 nmol/L) was observed in 4.1% of all women in the Multiple Outcomes of Raloxifene Evaluation study, ranging from 0% in south east Asia (very few patients) to 8.3% in southern Europe. Serum 25OHD was between 25-50 nmol/L in 24.3% of the women. Serum 25OHD showed a significant seasonal relationship, with lower values in all regions in winter. Serum PTH correlated negatively with serum 25OHD (r = -0.25; P < 0.001). This significant negative correlation was observed in all regions. When serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, mean serum PTH levels were 4.8, 4.1, and 3.5 pmol/L, respectively (by ANOVA, P < 0.001). Similarly, mean alkaline phosphatase levels were 83.7, 79.1, and 75.7 U/L (P < 0.001), respectively, with increasing serum 25OHD. The effect of serum 25OHD on BMD was only significant for the BMD of the trochanter where a serum 25OHD level less than 25 nmol/L was associated with a 4% lower BMD. After 6 months of treatment with vitamin D(3) (400-600 IU/day) and calcium (500 mg/day), serum 25OHD increased from 70.8 +/- 29.8 to 92.3 +/- 28.6 nmol/L. Serum PTH decreased significantly after 6 months of treatment, and this decrease depended on baseline serum 25OHD. When baseline serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, serum PTH decreased by 0.8, 0.5, or 0.2 pmol/L, respectively (P < 0.001). In conclusion, serum 25OHD was less than 25 nmol/L in 4% of the women, and this was associated with a 30% higher serum PTH. In 24% of the women serum 25OHD was between 25-50 nmol/L, associated with a 15% higher level of serum PTH compared with women with a serum 25OHD greater than 50 nmol/L. A low serum 25OHD level was also associated with higher serum alkaline phosphatase and lower BMD of the trochanter. Treatment with vitamin D(3) and calcium increased serum 25OHD and decreased serum PTH significantly; the effect was greater for lower baseline serum 25OHD.     

Bone mass and metabolism in women aged 45–55

OBJECTIVE Changes in calcium homeostasis and bone mass around the climacteric are poorly understood. We examined relations between endocrine factors and indices of bone mass and metabolism in healthy women approaching the menopause. DESIGN Cross-section study. PATIENTS Sixty-eight spontaneously menstruating women aged 45–55. MEASUREMENTS Bone density measured at lumbar spine (LS) and femoral neck (FN) using dual energy X-ray absorptiometry and distal non-dominant forearm using peripheral quantitative computed tomography. We recorded menstrual history, physical activity and dietary calcium, and measured serum calcium, phosphate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH, FSH and oestradiol (E₂), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion. RESULTS Using serum FSH level as a marker of ovarian function, 63 subjects could be classified into one of three groups: group A (serum FSH <10 U/l, n = 29), group B (10–35 U/l, n = 27) and group C (>35 U/l, n = 7). Bone density fell with declining ovarian function at the LS, FN and forearm trabecular (but not cortical) sites. Serum PTH was lower in group A vs B (mean (SD) 2.68 (0.97) vs 3.52 (1.17) pmol/l, P < 0.05), but similar to group C (2.90 (1.09) pmol/l, P = NS). Serum phosphate was elevated in group C compared to groups A and B (1.17 (0.15) vs 1.04 (0.11) and 1.05 (0.13) mmol/l, P < 0.05), and urinary PYD (61.1 (8.0) vs 50.4 (11.6) and 43.9 (8.1) μmol/mol creatinine) and DPD (15.9 (3.9) vs 12.0 (3.6) and 11.4 (3.6) μmol/mol creatinine) excretion were also increased. There were no significant differences in vitamin D metabolites or osteocalcin. Multivariate analysis suggested serum osteocalcin was positively related to physical activity and serum 1,25-dihydroxycholecalciferol levels. Serum free T3 was positively correlated with urinary DPD excretion, and inversely related to serum PTH. In all subjects, serum PTH was related to body weight (r = 0.38, P = 0.002). CONCLUSIONS Declining ovarian function before menopause is accompanied by reductions in bone mass and altered calcium metabolism. Free T3 may regulate bone resorption and indirectly modulate PTH release.     

ORIGINAL ARTICLE: Association between 25‐hydroxyvitamin D,somatic muscle weakness and falls risk in end‐stage renal failure

Objective Suboptimal levels of 25‐hydroxyvitamin D (25OHD) are common in haemodialysis patients (Chronic Kidney disease‐5D: CKD‐5D) and may be associated with reduced muscle strength and increased falls risk. We tested the hypothesis that 25OHD levels may be independently associated with falls risk in CKD‐5D. Background Supplementation with calcium and cholecalciferol reduces hip and other nonvertebral fractures in elderly individuals, and this effect may in part be attributable to reduction in falls frequency. The relationship between 25OHD and falls risk has not been investigated in CKD‐5D. Design and Patients This is a cross‐sectional study of 25 CKD‐5D patients with predialysis 25OHD, 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and intact parathyroid hormone (iPTH) measurement. Falls risk was assessed by quadriceps muscle strength, FallsScreen^© test (FST), Berg Balance Scale (BBS), timed ‘up and go’ (TUG) test, Modified Barthel Index (MBI) and Falls Efficacy Scale (FES). Results Mean age was 69·8 ± 12·1 years, and median time on dialysis was 3·1 years. Median 25OHD level was 55·3 nmol/l (range 20·8–125·8 nmol/l). Muscle strength was significantly positively correlated with 25OHD (P = 0·024) but not with 1,25(OH)₂D (P = 0·477) or PTH (P = 0·461). Statistically significant correlation between 25OHD levels and FST (P = 0·028) plus MBI (P = 0·0046) was noted. No significant correlation was detected between falls risk and 1,25(OH)₂D or PTH. Conclusions Suboptimal levels of 25OHD in CKD‐5D are associated with reduced quadriceps muscle strength and increased falls risk. 25OHD may be more important than the active renal metabolite 1,25(OH)₂D for muscle strength with implications for vitamin D choice and goals of supplementation. Further investigation is required to examine effectiveness of calciferol supplementation on the incidence of falls in CKD‐5D.     

Severe vitamin D deficiency in the institutionalized elderly

Severe vitamin D deficiency has been found to be prevalent in institutionalized elderly persons in several countries. The aim of the present work was to assess the vitamin D status of institutionalized elderly and compare it to that of community-living independent elderly in southern Greece during summer. Serum 25-hydroxyvitamin D [25(OH)D] and plasma PTH were measured in 58 (aged 68-103 yr, median 83.5) elderly inmates of a nursing home (IE) in the town of Kalamata (latitude N 37 degrees ) and in 48 (aged 60-89 yr, median 72) community-dwelling elderly (CDE) in Athens (latitude N 38 degrees ). The CDE had mean serum 25(OH)D 67.6 nmol/l [95% confidence interval (CI) 57.4 to 79.5], not far from the value of 80 nmol/l which is generally considered to be the lower limit of vitamin D sufficiency. The IE had significantly lower mean 25(OH)D 19.0 nmol/l (17.1 to 21.1); values of 25(OH)D below 20 nmol/l characterize severe vitamin D deficiency and may cause osteomalacia. The group of CDE had significantly lower mean plasma PTH 1.5 pmol/l (1.0 to 1.8) compared to 4.5 (3.9 to 5.3) of IE. Ninety percent of CDE had normal plasma PTH whereas 60% of IE had secondary hyperparathyroidism (PTH values >4.0 pmol/l). In conclusion, the majority of institutionalized elderly in southern Greece had severe vitamin D deficiency and secondary hyperparathyroidism in contrast to the fairly good vitamin D status and lack of hyperparathyroidism in the community-living elderly during summer. These findings indicate the need for vitamin D and calcium supplementation of the institutionalized elderly throughout the year.     

Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome

OBJECTIVE Parathyroid hormone-related protein (PTHrP) is recognized as a major pathogenetic factor of humoral hypercalcaemia of malignancy but Its action on vitamin D metabolism is controversial. Our aim was to study the relation between serum 1,25-dihydroxyvitamin D and humoral activity in malignancy-associated hypercalcaemia. DESIGN Prospective, cross-sectional, single-centre study of patients with documented solid malignancles, hypercalcaemia and suppressed plasma PTH concentrations. PATIENTS AND METHODS Vitamin D metabolites, PTH, nephrogenous cyclic AMP (N-CAMP), PTHrP and biochemical parameters of calcium and bone metabolism were measured in 39 patients with solid mallgnancles and hypercalcaemia and bone scans were performed. RESULTS In 27 patients plasma PTHrP levels were elevated (69%) and in 9 patients (23%) serum 1,25-(OH)₂D concentrations were not appropriately suppressed (>92pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1·6 pmol/l) had lower serum 1,25-(OH)₂,D concentrations than those with elevated levels (>1 6 pmol/l) (47±6 vs 70± 7 pmol/l, respectively; P < 0·04). Serum 1,25-(OH)₂D concentrations were higher in patients with negative bone scans than In those with metastatic bone disease (80 ± 9 vs 50 ± 5 pmol/l; P < 0·01) and similar levels of plasma PTHrP. In the patients with negative bone scans there was a significant relation between plasma PTHrP and serum 1,25(OH)₂,D (r= 0·51; P < 0·03) whereas there was no such correlation in those with a positive scan. CONCLUSION Contrary to current belief, serum 1,25-(OH)₂D concentrations are not generally suppressed in humoral hypercalcaemia of malignancy and PTHrP is a determinant of these levels in the absence of demonstrable bone metastases. These findings provide further Insights into the pathophysiology of malignancy-associated hypercalcaemia and may help in the clinical management of these patients.     

Vitamin D status, physical performance and body mass in patients surgically cured for primary hyperparathyroidism compared with healthy controls - a cross-sectional study

Objective Low plasma 25‐hydroxyvitaminD (25OHD) levels, reduced muscle strength and increased body mass index (BMI) are well‐known characteristics of primary hyperparathyroidism (PHPT). Mechanisms for low 25OHD levels, increased BMI and potential changes after parathyroidectomy are unknown. Muscle strength is reported to increase following surgical cure, but whether the improvement corresponds to healthy controls’ performances remains largely unknown. Patients We studied 51 patients with former PHPT [mean age 61(36–77) years] successfully treated by surgery [mean time since operation 7·4(5–15) years] and 51 sex‐ and age‐matched controls. Measurements Physical performance include “repeated chair stand” (RCS), “timed up and go” (TUG), muscle strength [hand grip, elbow flexion/extension and knee flexion/extension (60°/90°)], postural stability, biochemistry and anthropometric indices. Results Forty‐one cases had pathologically verified adenoma, three had hyperplasia and three had uncertain diagnosis whereas four had missing data. Dietary calcium intake, vitamin D supplementation and biochemistry including PTH and 25OHD levels did not differ between groups. Former patients had significantly higher BMI (28·8 ± 6·0 kg/m²) than controls (26·0 ± 4·7kg/m²). Muscle pain was more frequently reported by cases than controls, and cases performed RCS slower than controls (P = 0·02). Furthermore, female cases had lower muscle strength in knee flexion 60° (P = 0·02) and 90° (P = 0·05). Former patients no longer differed from controls after adjustment for BMI. Conclusion Following cure, 25OHD levels are normalized suggesting 25OHD insufficiency is not a constitutional characteristics in patients with PHPT. Increased BMI seems to be sustained. Whether this is caused by decreased muscle strength or reduced muscular performance causes adiposity needs further investigations.     

Bone mineral density increases with vitamin D repletion in patients with coexistent vitamin D insufficiency and primary hyperparathyroidism

Two hundred and twenty-nine consecutive subjects, 202 women and 27 men, referred for evaluation of osteoporosis or low bone mineral density (BMD) had serum measurements of immunoreactive PTH (iPTH) and 25-hydroxyvitamin D (25OHD) performed. Fifteen individuals (mean age +/- SE, 75+/-2.4 yr) had depressed serum 25OHD (<15 pg/mL) and concomitantly elevated (>65 pg/mL) iPTH levels. After successful treatment of vitamin D insufficiency in all subjects, iPTH remained inappropriately high or frankly elevated in 5, describing a 2.2% prevalence rate of coexistent primary hyperparathyroidism and vitamin D insufficiency in our population. Despite persistent primary hyperparathyroidism, normalization of serum 25OHD levels in these 5 subjects increased their BMD at an annual rate of 6.3% and 8.2% in spine and hip, respectively. Our results suggest that coexistent vitamin D insufficiency can obscure the diagnosis of primary hyperparathyroidism and, when treated effectively, can result in substantial short-terms gains in BMD despite persistence of the inappropriate production of PTH.