We hypothesized that losartan would help in achieving clinical remission in CED (Camurati Engelmann Disease) patients by blocking TGFB1(transforming growth factor beta 1) with fewer side-effects than steroids.
CED characterised by progressive diaphyseal dysplasia is associated with debilitating bone pain in the limbs, muscle weakness, fatiguability and waddling gait.[1] Clinical manifestations are due to mutations in the TGFB1 gene leading to its over-expression and effect on bone. Losartan is an antagonist of TGFB1 and it slows the progress of aortic root dilatation inMarfan’s syndrome by blocking the over-expression of TGFB1.[2] Steroids which have long been used for treatment of CED and been linked to long term side effects including those on growth, blood pressure and spinal osteoporosis.
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A 10 year old child with mutation is in exon 4, position C652T causing an R218C amino acid substitution on chromosome 19q13 had severe limitation of activity since 4 years of age due to pain in the limbs. She underwent a physical examination, a dual energy xray absorptiometry scan(DEXA), pain score and 6 minute walk test prior to the start of losartan with a repeat of the tests 9 and 17 months later. She is being treated with losartan at a dose of 0.75mg/kg/day. Table 1
Table 1
Table 1
Age at analysis(years) | 9.3 | 10.1 | 10.7 |
Cumulative pain score | 9 | 1.75 | 0.25 |
6 minute walk test(metres) | 171 | 405 | 414 |
DEXA weight(kgs) | 17.42 | 17.01 | 20.01 |
Height(cms) | 123.6 | 128.3 | 131.7 |
Fat(gms) | 1702 | 1253 | 2693 |
Lean(gms) | 14963 | 14957 | 16425 |
BMC(gms) | 754.9 | 805 | 890.2 |
A/G ratio | 0.29 | 0.23 | 0.39 |
Total body fat% | 10.2 | 7.7 | 14.1 |
BMD gm/cm2 | 0.845 | 0.873 | 0.887 |
Losartan improves the quality of life in children with CED by reducing the bone pain along with improvement in their activity levels, fat & muscle mass, without major effects on growth, blood pressure and spinal osteoporosis.
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