Heterotopic bone formation following total hip arthroplasty : clinical and experimental studies using NSAID and patelet-derived growth factor

Abstract: A consecutive series of 104 Lubinus IP arthroplasties was retrospectively studied with regard to heterotopic bone formation (HBF). Fifty-three cases were treated for 10 ± 2 days postoperatively with the NSAID oxyphenbutazone. Radiological follow up three months postoperatively showed significant HBF (;;,20mm) in 21 patients in the untreated and in none in the treated group (p<O.OOl). Some degree ofHBF was found in 9 of the treated patients and in 27 of those untreated (p<O.OOl). Since important factors in HBF development were kept constant in both groups, the difference in incidence of HBF was assumed to depend on the oxyphenbutazone treatment.In another retrospective series, all except 4 of 220 total hip arthroplasties were treated for about two weeks with oxyphenbutazone. Charnley (C), McKee-Farrar (M) and Bmnswik (B) arthroplasty were studied. The incidence ofHBF in the entire series was low (15%). Some degree ofHBF was seen in 37% (C), 8.3% (M) and 8.5% (B). Significant HBF (;;, 20mm) was seen in 30% (C), 4,8%(M) and 1,2% (B). Five years postoperatively,no significant functional differences were seen between the patients with HBF and those without HBF. Trochanter osteotomy (C) seemed to be the reason for the significantly higher incidence of HBF for C than for M and B, respectively (p<O.OOl).In a randomized, double-blind, placebo-controlled clinical study of 100 Lubinus SP Il arthroplasties diclofenac treatment (50mgx3) almost completely abolished substantial HBF (;;,20mm). In the placebo group, significant HBF was found in 3 3 of a total of 4 7 hips, compared to 1 of a total of 46 hips in the treated group (p<O.OOl). Functional scores 1-2 years postoperatively were not affected by HBF.PDGF (20 ng/ml) and induction of heterotopic new woven bone was studied in rats. The agent was administered locally and continuously for two weeks by means of mini-osmotic pumps inserted subcutaneously. The PDGF reached 6-mm long pieces of demineralized rat femur implanted into gluteal muscle pouches. Each rat had a contralateral control piece implanted. PDGF increased the ash-weights of the samples significantly (p<0.05).Using the same type of administration system, the effects ofa very small total dose (40 ng) of diclofenac on induction of new woven bone, were studied. The diclofenac treated samples showed significantly reduced ashweights (p<0.05).The effects of 0-200 11g diclofenac/ml after 48 h on the proliferation of cultured, serum starved human fibroblasts stimulated or not stimulated with PDGF, were studied using [3H]-thymidine. A dose-dependent inhibition was obvious at 211g/ml and significant at 5 11g/ml (p<0.05) both in the presence and in the absence of PDGF. The inhibiting effect occurred during the first 24 h of the PDGF-induced mitogenic signal. TRlTC-labelled phalloidin was used to study early and late effects of diclofenac on the organization of actin. Typical PDGF-induced changes of the actin cytoskeleton were inhibited by diclofenac. Diclofenac also caused the cells to assume a more epitheloidlike shape.The effects of diclofenac (50 l!g/ml) on whole cell appearance of human, serum starved fibroblasts, stimulated or not stimulated with PDGF, were studied using scanning electron microscopy. Cellular effects equivalentto the actin organization changes were detected at 15 min, 1 hand 48 h after administration of diclofenac. The morphological changes caused by diclofenac probably represent decreased cell motility.The extent of surgical trauma, and especially detachment of periosteum, seems to be the factor eliciting HBF after THA by activation of endogenous factors. NSA!Ds probably act prophylactically against HBF by inhibiting the recruitment of fibroblasts and their subsequent proliferation stimulated by PDGF and other growth factors.NSAID treatment for two weeks after THA and avoidance, if possible, of trochanter osteotomy is recommended for prophylaxis against HBF.