Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with reduced bone mineral density (BMD) mainly at sites rich in cortical bone. However, successful parathyroidectomy causes an increase in BMD especially at sites rich in trabecular bone. Plasma 25-hydroxyvitamin D (25OHD) levels are typically reduced and plasma 1,25-dihydroxyvitamin D [1,25(OH)(2)D] slightly increased in PHPT. These variations in vitamin D metabolites may influence variations in BMD and fracture risk. AIM: To investigate relations between preoperative vitamin D metabolites and skeletal consequences in patients with untreated PHPT and to appraise the influence of preoperative vitamin D metabolites on postoperative changes in BMD. Design Cross-sectional and cohort study. MATERIALS: Two hundred and forty-six consecutive Caucasian PHPT patients aged 19-91 years. (median 63, 87% females). RESULTS: BMD was reduced at the femoral neck (P < 0.001) and forearm (P < 0.001), but normal at the lumbar spine (P = 0.11). Levels of biochemical bone markers were associated with high plasma PTH, high plasma 1,25(OH)(2)D and low plasma levels of 25OHD. Moreover, low plasma 25OHD was associated with low levels of BMD at the femoral neck (r(p) = 0.23), the forearm (r(p) = 0.19) and the whole body (r(p) = 0.30), whereas plasma 1,25(OH)(2)D was inversely associated with BMD at all regional sites and the whole body. Plasma PTH only showed an inverse association with BMD at the forearm (r(p) = -0.21). No association was observed between biochemical variables and prevalent spinal fractures, all peripheral fractures or osteoporotic peripheral fractures. The annual increase in spinal BMD after surgery was positively associated with preoperative plasma PTH (r(p) = 0.40), whereas the annual increase in whole body BMD was inversely associated with plasma 25OHD (r(p) = -0.32). No change in BMD at the femoral neck and forearm was observed 1 year after surgery. CONCLUSION: Low vitamin D status and high plasma 1,25(OH)(2)D are associated with increased bone turnover and decreased BMD in patients with PHPT.

Plasma 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D is associated with parathyroid adenoma secretion in primary hyperparathyroidism: a cross-sectional study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with reduced plasma 25-hydroxyvitamin D (P-25OHD) and usually increased plasma 1alpha,25-dihydroxyvitamin D (P-1,25(OH)2D). Parathyroid tissue expresses the vitamin D receptor and it is thought that circulating 1,25(OH)2D participate in the regulation of parathyroid cell proliferation, differentiation and secretion. AIM: To investigate the relations between circulating levels of 1,25(OH)2D and 25OHD respectively and parathyroid adenoma weight (AW), plasma-parathyroid hormone (P-PTH) and PTH secretion expressed as P-PTH/AW. DESIGN: Cross-sectional study. MATERIAL: One hundred and seventy-one consecutive hypercalcaemic caucasian patients aged 19-87 years (median 63, 84% females) with surgically proven parathyroid adenoma. RESULTS: A weak positive correlation was found between P-25OHD and P-1,25(OH)2D (r=0.24, P<0.005). AW depended on sex and body mass index. Following adjustment, it was correlated positively to P-PTH, calcium (Ca) and alkaline phosphatase (AP) and inversely to plasma phosphate in a multiple regression model. AW was not associated with vitamin D metabolites. Preoperative P-PTH correlated positively to plasma levels of Ca and AP, but inversely to phosphate and 25OHD (P<0.001) levels. P-PTH was not associated with P-1,25(OH)2D (P=0.65). The P-PTH:AW ratio correlated inversely to P-25OHD (P<0.05), but showed no relations to plasma levels of Ca, phosphate or 1,25(OH)2D (P=0.22). CONCLUSION: In this material, low levels of 25OHD were related to higher levels of P-PTH and higher PTH:AW ratios in patients with PHPT suggesting that vitamin D deficiency increase PTH secretion activity. Neither PTH secretion nor AW was associated with circulating levels of 1,25(OH)2D.

Plasma 1,25-dihydroxyvitamin D levels in primary hyperparathyroidism depend on sex, body mass index, plasma phosphate and renal function.

BACKGROUND: Primary hyperparathyroidism (PHPT) is characterized by elevated plasma levels of PTH and calcium with reduced plasma phosphate. Physiologically, renal 1alpha,25-dihydroxyvitamin D [1,25(OH)(2)D] production is stimulated by PTH and phosphate deprivation, and inhibited by 1,25(OH)(2)D itself and calcium. AIM: To investigate relations between circulating levels of 1,25(OH)(2)D, 25-dihydroxyvitamin D (25OHD), PTH, calcium, phosphate, renal function and skeletal complications in patients with PHPT. DESIGN: Cross-sectional study. MATERIAL: Two hundred and fifty-two consecutive hypercalcaemic Caucasian patients aged 24-91 (median 65.9) years (85.3% females) with PHPT. RESULTS: In patients with PHPT, plasma 1,25(OH)(2)D was increased by 27%[107 (9-250) pmol/l, median (range)] compared to controls [84 (18-172) pmol/l, P < 0.001]. In univariate models, plasma 1,25(OH)(2)D depended inversely on age (r = -0.23, P < 0.001) and plasma phosphate (r = -0.23, P < 0.001) and positively on plasma calcium (r = 0.14, P < 0.05), plasma 25OHD (r = 0,15, P < 0.05) and creatinine clearance rate (r = 0.32, P < 0.001). In the final multiple regression model, plasma 1,25(OH)(2)D depended positively on renal function (r(p) = 0.43, P < 0.001) and female sex (r(p) = 0.15, P < 0.05) but inversely on body mass index (BMI; r(p) = -0.23, P < 0.005) and plasma phosphate (r(p) = -0.18, P < 0.05). Plasma 1,25(OH)(2)D correlated positively with renal calcium excretion and inversely with lumbar spine bone mineral density (BMD) but was not associated with risk of fractures or renal stones. CONCLUSION: Patients with PHPT have elevated plasma 1,25(OH)(2)D levels but, to a large extent, individual values overlap controls. The increase in plasma 1,25(OH)(2)D depends on renal function, hypophosphataemia and the female sex and is attenuated by high BMI. High plasma 1,25(OH)(2)D is associated with higher plasma calcium levels.

Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) and vitamin D insufficiency are common conditions that can occur in combination. However, low plasma 25-hydroxyvitamin D (25OHD) may also enhance the risk of PHPT or modify disease severity. AIM: To compare the risk of vitamin D insufficiency and deficiency stratified by age, sex and season between PHPT patients and controls and to assess associations between plasma 25OHD and adenoma weight, biochemical variables, bone mineral density (BMD) and clinical complications. DESIGN: Cross-sectional study. MATERIAL: A total of 289 consecutive Caucasian patients with PHPT aged 65.9 (24-92) years, 289 sex-, age- and season-matched normocalcaemic controls and 187 healthy adult blood donors. PHPT diagnosis was confirmed in 214 by neck exploration. RESULTS: Vitamin D insufficiency (plasma 25OHD < 50 nmol/l) was observed in 81% of PHPT patients compared with 60% of sex- and age-matched controls (P < 0.001) and 35% of blood donors (P < 0.001). During summer, 77%vs. 53% (P < 0.001) and 4% (P < 0.001), respectively, had vitamin D insufficiency. Average plasma 25OHD was 41 (range 9-87) nmol/l among 27 PHPT patients compared with 87 (21-173) nmol/l (P < 0.001) among aged-matched blood donors. During winter, 86%vs. 66% (P < 0.001) and 71% (P < 0.05), respectively, had vitamin D insufficiency. Vitamin D deficiency (plasma 25OHD < 25 nmol/l) was observed in 33% of PHPT patients compared with 20% of age- and sex-matched controls (P < 0.001) and 13% of blood donors (P < 0.001). Both PHPT patients and controls showed seasonal variations in 25OHD related to the average number of sun hours, but values were lower in PHPT patients at all calendar months. In PHPT patients low plasma 25OHD was associated with higher plasma levels of calcium, PTH and alkaline phosphatase and with lower renal calcium excretion, femoral neck and forearm BMD. No association was found between plasma 25OHD and adenoma weight (total or divided into tertiles). There was a trend towards increased risk of osteoporotic fractures (P < 0.08) with low plasma 25OHD. CONCLUSION: Vitamin D insufficiency and deficiency are common findings in PHPT and occur more often than in a sex- and age-matched control group referred from general practice and in normal blood donors irrespective of season. Low plasma 25OHD levels are associated with an aggravated clinical presentation of PHPT but do not affect adenoma size.