Relationship between serum 25-hydroxyvitamin D and parathyroid hormone in the search for a biochemical definition of vitamin D deficiency in children

Abstract

Background: Current guidelines use differing definitions of vitamin D deficiency based on serum 25-hydroxyvitamin D (25OHD) levels, which complicates clinical decision making on vitamin D doses used for the prevention and treatment. This study examined the natural relationship between serum 25OHD, parathyroid hormone (PTH), calcium, phosphate, and alkaline phosphatase. Methods: Two-hundred and fourteen children routinely admitted without conditions affecting the natural relationship among metabolites, including 17 with radiologically confirmed vitamin D deficiency rickets, were studied. The frequency of abnormal bone metabolites was examined for different 25OHD thresholds. results: The best fitting intersection point where PTH levels increased was a 25OHD level of 34 nmol/l (R 2 = 0.454; 95% confidence interval: 27-41 nmol/l). Seventy-three and 86% of the children demonstrated some biochemical abnormality below 25OHD levels of 41 and 27 nmol/l, respectively. All patients with rickets had 25OHD levels < 34 nmol/l. The vast majority of children with abnormal bone metabolites had 25OHD levels < 34 nmol/l and PTH levels > 50 ng/l. conclusion: Vitamin D deficiency, based on PTH elevation, was best defined by a 25OHD level of < 34 nmol/l. Because deficient calcium supply often coexists with vitamin D deficiency and both can independently cause nutritional rickets, a threshold for the skeletal effects of vitamin D should not be based purely on 25OHD levels. Vitamin D deficiency and its potential health implications are currently the subject of significant interest and controversy (1-6). However, what defines vitamin D deficiency is still under debate, in particular, in children, where studies are limited. The serum level of 25-hydroxyvitamin D (25OHD) is currently considered to be the most appropriate marker of the vitamin D status of an individual. Until recently, the conventional definition of vitamin D deficiency was a serum 25OHD level of < 25 nmol/l (<10 ng/ml) (7-9) as this level was associated with rickets or osteomalacia. However, the Pediatric Endocrine Society advocated a 25OHD level of < 37.5 nmol/l (<15 ng/ml) to define deficiency and < 50 nmol/l (20 ng/ml) to define insufficiency (10). More recently, the Institute of Medicine defined vitamin D sufficiency as a 25OHD level > 50 nmol/l (20 ng/ml) (11), whereas the Endocrine Society defined deficiency as a 25OHD level < 50 nmol/l (20 ng/ml), and insufficiency as a 25OHD level of 52.5-72.5 nmol/l (21-29 ng/ml), for both adults and children (12).These cutoff values were often based on adult studies in relation to fracture risk, intestinal calcium absorption, or bone mineral density (1,2,13-16). In addition, metabolic evidence supporting these chosen cutoff levels comes from the observations in adults that serum levels of parathyroid hormone (PTH) increase when serum 25OHD level decreases below a variably defined range of 37.5-75 nmol/l (15-30 ng/ml) (14,(16)(17)(18)(19)(20)(21). Active vitamin D (calcitriol) facilitates absorption of calcium and phosphorous fro...

Vitamin D and skeletal health in infancy and childhood

“…Although many clinical outcomes, including fracture and low BMD, have been linked with low circulating 25(OH)D, this remains an appropriate strategy in the absence of the definitive documentation of truly causal associations for such other conditions. Indeed, taken in the round, a threshold of 25nmol/l for deficiency, as suggested by the British Paediatric and Adolescent Bone Group [25], appears likely to prevent most cases of VDD rickets [28].…”

“…Similarly in children, extrapolation from a particular serum concentration of 25(OH)D to disease outcomes such as metabolic bone disease and secondary hyperparathyroidism cannot be made with any certainty. The inflection point at which parathyroid hormone (PTH) increases has been documented across a wide range of 25(OH)D concentrations (34-75nmol/l) [28][29][30], but an inverse relationship rather than a plateauing of PTH above a given 25(OH)D threshold is also observed in children and adolescents [31][32][33][34]. Furthermore, many children with low 25(OH)D do not develop rickets [28] and it is likely that an interaction between vitamin D and dietary calcium modifies the association between 25(OH)D and PTH, and subsequent clinical outcomes [35].…”

Evidence-Based Laboratory: Determining the Insufficiency Level of Vitamin D

“…D vitamini eksikliği ve bu durumun insan sağlığı üzerine olan etkileri tüm dünyanın ilgi odağında olup tartışılmaya devam edilmektedir (2)(3)(4)(5)(6)(7). Ancak D vitamini eksikliğinin tanımı hala tam olarak ortaya konulabilmiş değildir (8). Günümüzde bireyin D vitamini durumunu gösteren en uygun parametrenin 25-hidroksi vitamin D (25-OH D) olduğu kabul edilmektedir (8).…”

“…Ancak D vitamini eksikliğinin tanımı hala tam olarak ortaya konulabilmiş değildir (8). Günümüzde bireyin D vitamini durumunu gösteren en uygun parametrenin 25-hidroksi vitamin D (25-OH D) olduğu kabul edilmektedir (8).…”

Role of Parathormone in Parthenogenesis of Rickets

“…The main objective is to make calcium available for all body tissue metabolisms, mainly the brain and heart to maintain survival. PTH has been constantly high and moved to increase while calcium is still needed [5] Atapattu et al [10] have recently stated that vitamin D deficiency, based on PTH elevation, was best defined by a 25OHD level of <34 nmol/l. Because deficient calcium supply often coexists with vitamin D deficiency and both can independently cause nutritional rickets, a threshold for the skeletal effects of vitamin D should not be based purely on 25OHD.…”