The clinical features, investigation, treatment and outcome of two adults with fibrogenesis imperfecta ossium are described. In this rare acquired disorder of bone, normal lamellar collagen is replaced by structurally unsound collagen-deficient tissue, which leads to extreme bone fragility and ununited fractures. Transmission microscopy and SEM showed striking ultrastructural changes in bone structure and mineralisation. Both patients had monoclonal IgG paraproteins in the plasma and one excreted monoclonal lambda light chains in the urine. No abnormal plasma cells were found in the bone marrow and there was no evidence of amyloid deposition in the tissues. In both patients initial treatment with 1 alpha-hydroxycholecalciferol appeared to be ineffective, but in one, repeated courses of melphalan and corticosteroids over three years together with 1 alpha-hydroxycholecalciferol produced striking clinical and histological improvement. The findings in these and other patients strongly suggest that paraproteinaemia is an integral feature of fibrogenesis imperfecta ossium, and this needs further investigation.
Progressive structural scoliosis in growing rabbits has been produced. Tethering the thoracic spine into the form of an asymmetric lordosis produces a slowly progressive structural scoliosis by purely mechanical means. The addition of a contralateral release of the paraspinal muscles leads to a very progressive deformity with early cardiorespiratory failure. This release, however, was performed with an electric soldering iron and subsequent study showed that in those animals with severe progressive deformity there was localised spinal cord damage. We suggest that it is this neural damage and not the muscle release which leads to rapid progression. The clinical implications are important in that neurological dysfunction seems to render the spinal column less able to resist mechanical buckling and may be the crucial factor differentiating severely progressive from more benign curves.
One hundred and twenty-five patients with 194 feet affected by congenital talipes equinovarus were treated by the senior author during the period 1959 to 1980. Of these, 70 patients presented either at birth or in the early neonatal period, and 55 were seen later, having been referred from other centres. Seventy-five patients were subsequently reviewed by two of us; the remaining 50 were assessed from records and research files. Patients seen within four weeks of birth were termed "early", the remainder "late". Of the early group of 70 patients, 44 (with 68 affected feet) were reviewed and 26 (with 41 affected feet) were assessed from records. Excellent or good results were achieved in 94 per cent of feet treated conservatively and in 82 per cent of feet which required pantalar release. Of the 55 late referrals 32 patients (with 55 affected feet) were reviewed and 23 (with 30 affected feet) were assessed from records. Satisfactory results were slightly less frequent, but were achieved in 75 per cent of cases. There was no statistical correlation between early soft-tissue release and a good final outcome, but there was a positive statistical correlation between good clinical results and a high talocalcaneal index. Osseous correction (a laterally based wedge tarsectomy or a triple arthrodesis) was necessary at a later date in four feet (four per cent) of those who presented early and in 13 feet (15 per cent) of late referrals.
Six patients are described with idiopathic osteoporosis which began between the ages of 4 and 16 years. In four children the disorder was mild with pain in the back, vertebral collapse, qualitatively normal iliac bone biopsies, variable calcium balance and spontaneous recovery. The two remaining patients had progressive bone disease with deformity. One with a previously normal skeleton developed changes similar to those of osteogenesis imperfecta; in the other patient, who rapidly developed structural collapse associated with severe metaphysial osteoporosis, treatment was ineffective and the histological appearances of the bone suggested osteoblastic failure. Quantitative bone histology in four patients showed no evidence of excessive active resorption; and the ratio of Type III to Type I collagen in the skin was normal, in contrast to the findings in osteogenesis imperfecta. The significance of this study in relation to previous accounts is reviewed.
The clinical features of eight patients with myositis ossificans progressiva are described and the effects of treatment with the diphosphonate EHDP, together with surgical removal of ectopic bone, are assessed. Early correct diagnosis remains unusual, mainly because the significance of the short great toes is unrecognised, and because myositis may be mistaken for bruising, sarcoma or mumps. The diphosphonate disodium etidronate (EDHP) was given to all patients in an attempt to suppress calcification of new lesions; in five of them ectopic bone was removed during the treatment. EHDP sometimes delayed the mineralisation of newly formed bone matrix after surgical removal but this delay could not be predicted. The variable effect of EHDP may depend particularly on the amount absorbed and on the activity of new bone formation.
In a clinical, radiological and biochemical study of forty-two patients from Oxford with osteogenesis imperfecta, it was found that patients could be divided simply into mild, moderate and severe groups according to deformity of long bones. In the severe group (seventeen patients) a family history of affected members was uncommon and fractures began earlier and were more frequent than in the mild group (twenty-two patients); sixteen patients in the severe group had scoliosis and eleven had white sclerae; no patients in the mild group had white sclerae or scoliosis. Radiological examination of the femur showed only minor modelling defects in patients in the mild group, whereas in the severe group five distinct appearances of bone (thin, thick, cystic and buttressed bones, and those with hyperplastic callus) were seen. The polymeric (structural) collagen from skin was unstable to depolymerisation in patients in the severe group, but normal in amount, whereas the reverse was found in the mild group. This division according to long bone deformity may provide a basis for future research more useful than previous classifications.
1. The phosphonates are simple chemical compounds containing P-C-P bonds which are resistant to the action of naturally occurring phosphatases and pyrophosphatases. They inhibit the formation and dissolution of apatite crystals 2. In man one diphosphonate (EHDP) has been shown to reduce the excessive turnover of bone in Paget's disease and also appears to slow the mineralisation of ectopic bone matrix in myositis ossificans progressiva. 3. The possible uses of the diphosphonates in bone disorders with excessive resorption and in ectopic mineralisation are being further investigated.
