Redefining vitamin D insufficiency
Authors: A Malabanan, IE Veronikis, MF Holick
Journal: The Lancet (1998)

Vitamin D deficiency causes secondary hyperparathyroidism which can lead to osteomalacia, irreversible bone loss,1Parfitt AM Rao DS Stanciu J Villanueva AR Kleerekoper M Frame B Irreversible bone loss in osteomalacia: comparison of radial photon absorptiometry with iliac bone histomorphometry during treatment.J Clin Invest. 1985; 76: 2403-2412Crossref PubMed Scopus (106) Google Scholar and increased risk of fracture.2Chapuy MC Arlot ME Duboeuf F et al.Vitamin D3 and calcium to prevent hip fractures in elderly women.N Engl J Med. 1992; 327: 1637-1642Crossref PubMed Scopus (2692) Google Scholar, 3Dawson-Hughes B Harris SS Krall EA Dallal GE Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.N Engl J Med. 1997; 337: 670-676Crossref PubMed Scopus (1944) Google Scholar Vitamin D deficiency is not well characterised and varying 25-hydroxyvitamin D (25[OH]D) thresholds have been used.4McKenna MJ Differences in vitamin D status between countries in young adults and the elderly.Am J Med. 1992; 93: 69-77Summary Full Text PDF PubMed Scopus (573) Google Scholar, 5Villareal DT Civitelli R Chines A Avioli LV Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass.J Clin Endocrinol Metab. 1991; 72: 628-634Crossref PubMed Scopus (229) Google Scholar We evaluated the effect on blood concentrations of parathyroid hormone (PTH) by increasing 25(OH)D levels above 25 nmol/L with vitamin D therapy. The first 35 patients (mean age 67 [SD 8] years; range 49–83 years) with 25(OH)D levels greater than 25 nmol/L and less than 62·5 nmol/L (reference range, Nichols Institute, San Juan Capistrano, CA, USA, 22·5–130 nmol/L), and without malabsorption, hypercalcaemia, or alcohol abuse, were prescribed 50 000 IU of oral vitamin D2 once a week for 8 weeks and 1000–1500 mg calcium daily. Serum 25(OH)D, intact PTH immunoradiometric association (reference range, Nichols, 10–65 pg/mL), and calcium concentrations (reference range, Nichols, 2·20–2·53 mmol/L) were measured before and after treatment, assessed using paired t-tests with two-tailed p values, and presented as mean (SE). After treatment, 25(OH)D levels rose 109% (42·5 [2·5] to 87·5 [2·5] nmol/L) and PTH values decreased 22% (63 [5] to 45 [3] pg/mL) (figure A). Calcium did not change (2·33 [0·03] to 2·35 [0·03] mmol/L, p=0·31). 40% overall had secondary hyperparathyroidism (PTH <65 pg/mL). Serum PTH values were evaluated with respect to stratified pre-treatment 25(OH)D levels (figure B). After vitamin D and calcium therapy, PTH decreased by 35% (80 [12] to 48 [6] pg/mL, p<0·02) for 25(OH)D levels of 27·5–39·9 nmol/L (n=11, 55% had secondary hyperparathyroidism) and by 26% (57 [5] to 41 [5] pg/mL, p<0·001) for 25(OH)D values of 40–49·9 nmol/L (n=17; 35% had secondary hyperparathyroidism). For 25(OH)D of 50 to 60 nmol/L (n=7), PTH decreases were not significant although 25(OH)D levels increased by 66%. Notably, in patients without secondary hyperparathyroidism (n=16) (pre-treatment 25(OH)D levels of 27·5–47·5 nmol/L), PTH still decreased by 22% (47 [3] to 37 [5] pg/mL, p<0·01). Adults over the age of 49 years may require a serum 25(OH)D of at least 50 nmol/L to achieve the optimum PTH levels. When 25(OH)D levels were below 50 nmol/L, PTH tended to increase, potentially resulting in increased bone calcium mobilisation and accompanying bone loss. After reviewing 169 patients seen in our bone health clinic (86% women, 14% men; average age is 62 [16] years), 41% were found at risk for vitamin D deficiency with 25(OH)D concentrations less than 50 nmol/L. Therefore, secondary hyperparathyroidism as well as inappropriately high normal PTH levels exist in patients (ages 49–83 years) with 25(OH)D levels previously believed to be sufficient. 50 nmol/L should be considered the minimum 25(OH)D value for vitamin D sufficiency in this age group. Therapy with 50 000 IU of oral vitamin D2 weekly for 8 weeks along with supplemental calcium safely and effectively corrects secondary hyperparathyroidism, potentially leading to decreased fracture risk in the elderly.