Clinical Endocrinology (1977) 7, Suppl., 245s-246s.
O R A L l a - H Y D R O X Y V I T A M I N D, I N T H E TREATMENT OF OSTEOMALACIA ASSOCIATED WITH MALABSORPTION JULIET E. COMPSTON, L.W.L. HORTON A N D J.R. TlGHE Gastrointestinal Laboratory, Rayne Institute, and Department of Surgical Pathology, St. Thomas 'Hospital, London
Oral la-hydroxyvitamin D3 (Ia-OHD:,) has been shown to be effective in the treatment of some patients with renal osteodystrophy (Coburn er al., 1976), but its long-term use in osteomalacia associated with malabsorption has not been reported. We describe a patient with massive small intestinal resection and severe osteomalacia who showed a good symptomatic, biochemical, and histoloacal response to small doses of oral la-OHD3. The patient, a housewife, now aged 3 3 years, underwent resection of all small intestine excepting 3 0 c m of jejunum following a volvulus in 1971. Osteomalacia was diagnosed in 1973. Details of subsequent treatment, and timing of bone biopsies, are shown in Fig. I . Serum calcium and phosphate concentrations were initially normal and remained so throughout treatment. The elevated serum alkaline phosphatase concentration returned to normal for the first time seven months after treatment with la-OHD3 was started. After nearly 2 years of p a r e n t e d vitamin D2 therapy calcification fronts, initially almost absent, had become normal, but osteoid volume, although showing some reduction remained abnormally elevated. After 6 months la-OHD3 therapy osteoid volume had become normal, and bone pain, present for the previous three years, had disappeared. The excellent response to oral la-OHD3 in this patient, despite the presence of only 3 0 cm of jejunum, indicates that sufficient intestinal absorption of the analogue occurred to produce therapeutic blood levels and t o promote bone healing, even at the relatively small dose used. Oral therapy is more acceptable to most patients than p a r e n t e d therapy, and the speed and degree of response to oral la-OHD3 compared favourably to that seen following p a r e n t e d vitamin D2 treatment, even though the weight equivalent of the latter was 215 times greater. Hypercalcaemia has not been a problem in our patient, but when it occurs it can be much more rapidly reversed after treatment with la-OHD, than with the parent vitamin (Kanis & Russell, 1977). Thus oral la-OHD3 may prove t o be of value in the treatment of osteomalacia associated with midabsorption.
Correspondence: Dr J . E. Compston. Gastrointestinal Laboratory, St. Thomas' Hospital, London SE 1 .
245s
Juliet E. Compston, L . W . L . Horton and J. R. Tighe
246s
_Osteoid volume % total bone volume C o l c i f icotion fronts % ostcoid surface
k k L
a'
40 0
1973 1974
1975
1976
1977
Fig. 1 . Details of response of serum alkaline phosphatase, osteoid volume, and calcification fronts to various forms of vitamin D therapy. Bone biopsies were carried out in January 1973, March 1975, November 1975, and May 1976. The interrupted horizontal line indicates the upper limit of normal for serum alkaline phosphatase (13 KA unitddl). Osteoid volume and calcification fronts were measured quantitatively on undecalcified sections using both a 'Quantimet' 720 automated image-analyser and an eye-piece graticule. REFERENCES COBURN, J.W., HARTENBOWER. D.L. & BRICKMAN, A S . (1976) Advances in vitamin D metabolism as they pertain to chronic renal disease. American Journal of CIinical Nutrition, 29, 1283-1299. KANIS. J.A. & RUSSELL, R.C.G. (1977) Rate of reversal of hyparcalcaemia and hypercalciuria induced by vitamin D and its lahydroxylated derivatives. British Medical Journal, i, 78-81.
O R A L l a - H Y D R O X Y V I T A M I N D, I N T H E TREATMENT OF OSTEOMALACIA ASSOCIATED WITH MALABSORPTION JULIET E. COMPSTON, L.W.L. HORTON A N D J.R. TlGHE Gastrointestinal Laboratory, Rayne Institute, and Department of Surgical Pathology, St. Thomas 'Hospital, London
Oral la-hydroxyvitamin D3 (Ia-OHD:,) has been shown to be effective in the treatment of some patients with renal osteodystrophy (Coburn er al., 1976), but its long-term use in osteomalacia associated with malabsorption has not been reported. We describe a patient with massive small intestinal resection and severe osteomalacia who showed a good symptomatic, biochemical, and histoloacal response to small doses of oral la-OHD3. The patient, a housewife, now aged 3 3 years, underwent resection of all small intestine excepting 3 0 c m of jejunum following a volvulus in 1971. Osteomalacia was diagnosed in 1973. Details of subsequent treatment, and timing of bone biopsies, are shown in Fig. I . Serum calcium and phosphate concentrations were initially normal and remained so throughout treatment. The elevated serum alkaline phosphatase concentration returned to normal for the first time seven months after treatment with la-OHD3 was started. After nearly 2 years of p a r e n t e d vitamin D2 therapy calcification fronts, initially almost absent, had become normal, but osteoid volume, although showing some reduction remained abnormally elevated. After 6 months la-OHD3 therapy osteoid volume had become normal, and bone pain, present for the previous three years, had disappeared. The excellent response to oral la-OHD3 in this patient, despite the presence of only 3 0 cm of jejunum, indicates that sufficient intestinal absorption of the analogue occurred to produce therapeutic blood levels and t o promote bone healing, even at the relatively small dose used. Oral therapy is more acceptable to most patients than p a r e n t e d therapy, and the speed and degree of response to oral la-OHD3 compared favourably to that seen following p a r e n t e d vitamin D2 treatment, even though the weight equivalent of the latter was 215 times greater. Hypercalcaemia has not been a problem in our patient, but when it occurs it can be much more rapidly reversed after treatment with la-OHD, than with the parent vitamin (Kanis & Russell, 1977). Thus oral la-OHD3 may prove t o be of value in the treatment of osteomalacia associated with midabsorption.
Correspondence: Dr J . E. Compston. Gastrointestinal Laboratory, St. Thomas' Hospital, London SE 1 .
245s
Juliet E. Compston, L . W . L . Horton and J. R. Tighe
246s
_Osteoid volume % total bone volume C o l c i f icotion fronts % ostcoid surface
k k L
a'
40 0
1973 1974
1975
1976
1977
Fig. 1 . Details of response of serum alkaline phosphatase, osteoid volume, and calcification fronts to various forms of vitamin D therapy. Bone biopsies were carried out in January 1973, March 1975, November 1975, and May 1976. The interrupted horizontal line indicates the upper limit of normal for serum alkaline phosphatase (13 KA unitddl). Osteoid volume and calcification fronts were measured quantitatively on undecalcified sections using both a 'Quantimet' 720 automated image-analyser and an eye-piece graticule. REFERENCES COBURN, J.W., HARTENBOWER. D.L. & BRICKMAN, A S . (1976) Advances in vitamin D metabolism as they pertain to chronic renal disease. American Journal of CIinical Nutrition, 29, 1283-1299. KANIS. J.A. & RUSSELL, R.C.G. (1977) Rate of reversal of hyparcalcaemia and hypercalciuria induced by vitamin D and its lahydroxylated derivatives. British Medical Journal, i, 78-81.
