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.


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).


METHODS
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 to 101.75 +/- 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).


CONCLUSIONS
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.
Krishnamoorthy
Geetha
G
Department of Biochemistry, Lokmanya Tilak Municipal Medical College and Hospital, Sion, Mumbai - 400 022, India.
Nair
Rahul
R
Sundar
Uma
U
Kini
Prayag
P
Shrivastava
Makardhwaj
M
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000927:Anticonvulsants / Q000009:adverse effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002118:Calcium / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage*; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D010018:Osteomalacia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D010672:Phenytoin / Q000009:adverse effects*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D013997:Time Factors; D014635:Valproic Acid / Q000009:adverse effects*; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood; D055815:Young Adult
D000927:Anticonvulsants; D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D014807:Vitamin D; D014635:Valproic Acid; D010672:Phenytoin; D000469:Alkaline Phosphatase; D002118:Calcium