Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dosage: A prospective study

Background: Long-term therapy with antiepileptic drugs (AED) may be associated with increased total serum alkaline phosphatase (ALP) levels and reduced serum calcium, inorganic phosphorous, and vitamin D levels. These adverse biochemical alterations have an adverse effect on bone health
Objective: To determine (a) onset of derangements in serum total ALP and its isoenzymes (liver, bone), calcium and 25-hydroxy vitamin D (25-OHD) concentrations after initiation of treatment with phenytoin or valproic acid monotherapy and (b) the effect of simultaneous supplementation with calcium and 25-OHD at recommended daily allowance (RDA) dosage, on these biochemical parameters.
Materials and Methods: Study was a prospective, case-controlled study in adults. Serum biochemical parameters were estimated at baseline, 30, 60, and 90 days of starting AED treatment in the study subjects: Groups--A (only calcium supplementation) and Group B (both calcium and 25-OHD supplementation).
Statistical Analysis: Mean±SD, and students′ paired t test (between groups A and B) unpaired students′ t test (drug-wise).
Results: At 60 days of AED therapy Group A showed a significant increase in serum total ALP (78.83±11.04 to101.75 ± 9.56 IU/l) (P < 0.001), ALP-liver isoenzyme, (41.97± 10.81 to 68.83 ±7.81 IU/L) (P < 0.001), significant decrease in calcium (9.30 ± 0.36 to 8.80 ± 0.38 mg%) (P < 0.001), ALP-bone isoenyzme (36.84 ± 5.01 to 32.92 ± 6.46 IU/L) (P < 0.001), and a significant decrease in 25-OHD (25.19 ± 5.98 to 19.76 ± 5.35 ng/ml) (P < 0.001) at 90 days. In contrast Group B, at 60 days, showed a significant decrease in serum total ALP (81.92 ± 19.63 to 54.77. ± 11.53 IU/L) (P < 0.0001), ALP-liver isoenzyme (48.01. ± 13.53 to 28.12. ± 5.88 IU/L) (P < 0.0001), significant increase in calcium ((9.24 ± 0.31 to 9.93 ± 0.26 mg%) (P < 0.001) and ALP-bone isoenzyme levels (33.93 ± 12.2 to 26.25 ± 8.23 IU/L). In Group B, 25-OHD levels showed a significant increase at 90 days (24.36 ± 3.42 to 31.53 ± 327 ng/ml) (P < 0.0001).
Conclusion: Biochemical derangements in calcium metabolism involving the bone are seen by 60 days after starting AED monotherapy, indicating predisposition to development of osteomalacia in these patients. This is preventable by simultaneous oral supplementation with calcium and 25-OHD.

Keywords
Anticonvulsant drug, bone metabolism, supplemental calcium and vitamin D