Alterations in vitamin D metabolites during treatment of paget's disease of bone with calcitonin or etidronate
Authors: Ms. Devlin Rowena D. , Gutteridge Donald H. , Prince Richard L. , Retallack Robert W. , Worth Graeme K. 
Published: February 2010

We report serum 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in untreated Paget's disease and the effect of treatment with either calcitonin (CT) or etidronate (EHDP) on these levels.

In untreated Paget's patients serum 25-OHD (73 ± 29 nmol/liter, n = 36, mean ± SD) and 24,25-(OH)2D (0.3–12.9 nmol/liter, median 2.2, n = 36) levels were significantly lower than in age-matched controls (94 ± 30 nmol/liter, n = 32, p &lt; 0.005, and 1.3–16.4 nmol/liter, median 5.3; n = 32, p &lt; 0.001, respectively). Also, the 24,25-(OH)2D levels correlated with the 25-OHD levels in the untreated Paget's patients (r = 0.56, p &lt; 0.01) and in the controls (r = 0.39, p &lt; 0.05). The percentage molar ratio of 24,25-(OH)2D to 25-OHD in Paget's patients had a median value of 3.7% (range 0.4–14.3%), which was not significantly different from controls, who had a median value of 5.6% (range 2.2–18%). There was no difference between the 1,25-(OH)2D, and immunoreactive PTH (iPTH) levels of Paget's patients and control subjects. The percentage molar ratio of 1,25-(OH)2D to 25-OHD in untreated Paget's patients (0.157 ± 0.09%) was not significantly different from controls (0.124 ± 0.05%) despite lower 25-OHD levels in Paget's patients. There was a significant inverse correlation between the severity of Paget's disease as measured by plasma alkaline phosphatase (AP) levels and 25-OHD levels (r = 0.392, p &lt; 0.02); however, 24,25-(OH)2D and 1,25-(OH)2D levels were not correlated with AP. No correlation was found between any vitamin D metabolite and AP levels in control subjects.

Three treatment groups of Paget's patients were studied: (1) oral EHDP treatment (up to 6 months), in which plasma corrected calcium (Cacorr) fell but serum ionized calcium (Ca2+) and plasma total calcium (Ca) remained unchanged. Plasma AP fell significantly with treatment, and serum 1,25-(OH)2D levels increased significantly. The already low 24,25-(OH2D levels (compared with control values) fell further with treatment. (2) Short-term (CT) treatment (up to 18 months) showed a significant decrease in AP and Cacorr but not in Ca2+ or Ca. Again, serum 1,25-(OH)2D levels increased significantly compared to pretreatment values, but 24,25-(OH)2D levels were unchanged. (3) Long-term CT treatment (between 20 months and 8 years), in which the only significant changes observed were a fall in AP and a rise in Ca. In all three treatment groups, serum iPTH, Ca2+, 25-OHD, and plasma phosphate were unchanged with therapy.

We conclude that Paget's disease is associated with alterations in vitamin D metabolite levels and that treatment with either CT or EHDP results in further changes in these levels, with no change in iPTH or Ca2+. Mediation by iPTH levels and the various indices of serum calcium appear unable to adequately explain these marked alterations in vitamin D metabolite levels. Thus a more extensive investigation of vitamin D metabolism in Paget's disease is warranted.