D-Penicillamine alters the normal metabolism of collagen by inhibiting cross-linking and protein synthesis. This could affect wound healing, accelerate skin thinning and possibly exaggerate the osteoporosis of rheumatoid disease. The mean time to wound healing after 42 orthopaedic surgical operations in 21 patients treated with penicillamine was 19.8 (+/- 13.1) days. Compared with an earlier study, these results suggest that the drug has a comparable effect on would healing to corticosteroids given for three years. Skinfold thickness over the fourth metacarpal of the dominant hand was measured in 28 cases before and during penicillamine treatment. There was a significant decrease both in the first and second four-month periods of treatment (P less than 0.005 and P less than 0.01). Corticosteroids in constant dose did not have an additive effect. In view of the wound healing findings the significance of these results must await further sequential measurements. The normal progression of osteoporosis over three years was documented in 70 patients who had not received penicillamine. Penicillamine reversed this trend in 35 patients after one year of treatment (P less than 0.005). The results confirm that the osteoporosis is related to disease severity rather than drug therapy.

Collagen biosynthesis was measured in skin biopsies taken from 13 patients with rheumatoid arthritis before and after at least 6 months' continuous treatment with D-penicillamine, 1.0 g/day. There was a significant 36% reduction in mean collagen biosynthesis (p less than 0.0125) as assayed by 14C-hydroxyproline formation from 14C-proline during 24 h of tissue culture. The changes in 14C-hydroxyproline formation were correlated with the total doses of D-penicillamine taken (r = 0.71, p less than 0.01) and the falls in ESR (r = 0.72, p less than 0.01). No significant change in general protein syntehsis was observed. 500 microgram/mlD-penicillamine added to skil cultures in vitro inhibited both collagen and general protein synthesis (p less than 0.01). It is suggested that the clinical improvement induced by D-penicillamine could reflect an inhibition of collagen proliferation in the synovium.

Bone density was studied in ten patients before and after release of an idiopathic carpal tunnel syndrome. A corticomedullary ratio was measured at the mid-point of the metacarpals and proximal phalanges of both hands. There was a significant increase in the mean bone density over the period of observation in the thumb and middle finger metacarpals and in the index, middle, and ring finger proximal phalanges of the operated hand. There was no significant increase in the density of either metacarpal or proximal phalanx on the non-operated side. Release of the carpal tunnel syndrome provides not only symptomatic relief but also leads to increased bone density.

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