Update on vitamin D: pros and cons.

Controversies on vitamin D currently represent a challenging topic in mineral metabolism research. In particular, current guidelines on vitamin D supplementation did not report consistent recommendation and the issue related to beneficial vs harmful effects of loading vitamin D doses did not lead to any firm universal conclusion. Finally, serum and clinical outcomes of vitamin D supplementation, particularly as far as extra-skeletal effect of the hormone, need to be further investigated.

Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D. CLINICAL CASE: Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection. CONCLUSIONS: We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Management of endocrine disease: value and limitations of assessing vitamin D nutritional status and advised levels of vitamin D supplementation.

The growing attention to the role of vitamin D in skeletal and extra-skeletal diseases over the last decade induced an increased demand for vitamin D determination as well as a dramatic rise of sales of vitamin D supplement. However, several critical points in this field remain to be clarified. We lack a clear consensus about the definition of vitamin D deficiency, insufficiency, and sufficiency. The identification of different thresholds defining vitamin D status has relevant implications in clinical practice. In fact, the worldwide prevalence of low vitamin D status is highly varying according to the level of 25(OH)D utilized to define sufficiency. Therefore, the assessment of 25-hydroxyvitamin D levels may have a critical role, but a number of different technical problems associated with its determination may interfere in interpreting the results. The hydrophobic nature of vitamin D and the tight binding to its carrier (vitamin D binding protein), the different forms circulating in blood, and the issue of standardization are among the most important factors influencing the measurement of this metabolite. Another controversial point relies on the conflicting guidance on prevention and treatment of vitamin D deficiency endorsed by different medical and scientific communities. In particular, uncertainty exists about how to replete vitamin D stores, how to maintain normal 25(OH)D levels after repletion, which form of vitamin D is preferable for supplementation, and which route of administration and dosing regimens are advisable. Finally, concerns have been raised regarding vitamin D toxicity and its adverse effects.

Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis.

CONTEXT: We previously showed that a single high dose of oral (po) cholecalciferol (D3) sharply increases serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: We evaluated the long-term bioavailability and metabolism of a single po or intramuscular (im) high dose of ergocalciferol (D2) or D3. DESIGN: This was a prospective intervention study. SETTING: The study was conducted in an ambulatory care setting. PATIENTS: Participants were 24 subjects with hypovitaminosis D. INTERVENTIONS: A single dose of 600,000 IU of po or im D2 or D3 was administered. MAIN OUTCOME MEASURES: Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured at baseline and at days 30, 60, 90, and 120 by RIA. Serum 1,25(OH)2D2, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-hydroxyvitamin D2 [24,25(OH)D2], and 24,25-hydroxyvitamin D3 [24,25(OH)D3] were measured by liquid chromatography-tandem mass spectrometry in a subgroup of patients receiving the po formulations. RESULTS: The areas under the curve of 25(OH)D after D3 were significantly higher than those after D2 (P < .0001). Serum 25(OH)D basal difference significantly increased at day 30 with po D2 and D3 (P < .01 and P < .0001) and up to day 90 with po D3 (P < .01). The im formulations produced a slow increased, and values peaked at day 120 relative to the other time points (P < .0001). We found a decrease in 1,25(OH)2D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)2D2 at day 30 (P < .01) and up to day 120 (P < .01) after po D2. Oral D2 and D3 produced increases in 24,25(OH)D2 and 24,25(OH)D3, respectively, at day 30 (P < .001). CONCLUSIONS: A po dose of 600,000 IU of D2 or D3 is initially more effective in increasing serum 25(OH)D than the equivalent im dose and is rapidly metabolized. Our RIA assay for 1,25(OH)2D may not recognize 1,25(OH)2D2.

Metabolic changes following 500 µg monthly administration of calcidiol: a study in normal females.

This study was performed to investigate the effect of monthly oral administration of 500 µg of calcidiol (25-hydroxyvitamin D(3)) for 4 months on both serum vitamin D levels and sequential changes of parameters of calcium metabolism; 18 normal women aged 24-72 years were investigated. There was a significant increase of serum 25(OH)D after the first administration; thereafter all values persisted significantly higher compared to the basal value (P < 0.001). Mean 1,25(OH)(2)D serum levels peaked at day 3 and then tended to stabilize following day 30. During the first month, all mean values observed following the initial administration were significantly higher than basal values. The first calcidiol dose produced a significant reduction of serum PTH levels (P < 0.001), which then remained constant over time. Concerning serum calcium and phosphorus, we were not able to demonstrate any significant change during the entire observation period. Considering the single values for both serum ionized and total calcium, the values of Ca(2+) exceeded upper limits of normal on only two occasions. Regarding biochemical markers of bone remodeling, mean changes of serum bone isoenzyme of alkaline phosphatase activity showed a significant trend to decrease, starting at day 30. No significant changes of serum CTX values were noted. Overall, 24-h urinary excretion of calcium did not change, seven values exceeding the threshold of 4 mg/kg body weight. Monthly administration of 500 µg of 25-hydroxyvitamin D(3) may be considered an alternative for vitamin D repletion, without any detrimental effect.

The effects of alendronate treatment in osteoporotic patients affected by monoclonal gammopathy of undetermined significance.

In patients with monoclonal gammopathy of undetermined significance (MGUS) the increase of bone turnover rate can increase the risk of fracture. Thus, a treatment normalizing this negative balance could be of benefit in these patients. We studied 100 patients affected by MGUS, grouped according to the presence (group A, 50 patients) or absence (group B) of vertebral fractures and/or osteoporosis. Group A was treated with alendronate (70 mg/weekly) plus calcium and cholecalciferol for 18 months, and group B was treated with calcium and cholecalciferol. After 18 months, the mean bone mineral density (BMD) of the lumbar spine and total femur had increased by 6.1% and 1.5%, respectively, in group A. In the nine patients of this group not taking alendronate, BMD values of the lumbar spine and total femur decreased by 1.6% (P < or = 0.001 ) and 1.3% (P < or = 0.01), respectively. In patients of group B, BMD increased by 1.2% at the lumbar spine and decreased by 1.2% at the total femur. Corresponding figures of those patients in the same group not taking calcium and vitamin D supplementation were -0.1% and -1.2%, respectively. At 18 months we observed significant decreases of serum bone markers: the difference between the groups was -23.2 (P < or = 0.01) for bone alkaline phosphatase, -23.6 for osteocalcin (P < or = 0.01), -35.1 for C-terminal telopeptides of collagen type I (P < or = 0.001), and -0.47 for bone sialoprotein (P = nonsignificant). Treatment with alendronate could lead to a significant reduction in fracture risk in MGUS patients with skeletal fragility.