Herbal Fufang Xian Ling Gu Bao prevents corticosteroid-induced osteonecrosis of the femoral head—A first multicentre, randomised, double-blind, placebo-controlled clinical trial

Abstract

Background/ObjectiveThis is a multicentre, randomised, double-blind, placebo-controlled clinical trial to investigate the safety and efficacy of Chinese herbal Fufang Xian Ling Gu Bao (XLGB) with antiadipogenic compounds for the prevention of corticosteroid (CS)-induced osteonecrosis of femoral head (ONFH).MethodsPatients of both genders, aged between 18 and 65 years, with diseases such as systemic lupus erythematosus, nephrosis, dermatosis and rheumatoid arthritis indicated for CS treatment and who did not show magnetic resonance imaging of ONFH at baseline were recruited into the study and then randomised into either XLGB group (n = 129) with daily oral administration of XLGB or placebo group (n = 146).ResultsMagnetic resonance imaging revealed a total of 30 ONFH cases at 6 months after CS treatment, with 6.98% (9 of 129 cases) and 14.4% (21 of 146 cases) in the XLGB group and placebo group, respectively, (p < 0.05), i.e., a 2-fold significantly less ONFH identified in the XLGB treatment group. Blood tests suggested that XLGB significantly inhibited the elevation of activated protein C resistance induced by CS treatment.ConclusionThis is the first multicentre clinical study to demonstrate that the antiadipogenic compounds–rich herbal Fufang (formula) XLGB is effective in preventing CS-associated ONFH in patients with immune-inflammatory diseases under CS treatment.The translational potential of this articleThe translation potential of this clinical trial is that the initially officially approved clinical indication for XLGB for treatment of osteoporosis has been now also proven to be effective for a new clinical application.

Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model

“…SAON is a common orthopaedic disease occurring after pulsed/long term corticosteroids (CS) treatment for infectious diseases (such as severe acute respiratory syndrome, SARS) and rheumatoid diseases (such as rheumatoid arthritis, systemic lupus erythematosus, SLE) [6][7][8]. The occurrence of SAON is highly associated with the dosage and duration usage of CS.…”

Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients

“…On the other hand, few randomised clinical trials concerning ONFH can be followed up for a long term. Published studies mostly reported their results after a follow-up duration of only 2 or 3 years [4,33,40], but the previous study had reported that the interval between diagnosis and collapse could be over 4 years in 46% of cases [41]. In comparison to the natural collapse rate of 49% reported by a systematic review that included the most hips with ONFH [27], our study observed a collapse rate of 26% based on prolonged follow-up data, supporting that HGF helps prevent the natural disease progression of ONFH.…”

“…Osteonecrosis of the femoral head (ONFH) in SARS survivors could be attributed to the steroid because high cumulative doses of steroids were closely associated with the occurrence of osteonecrosis [3]. Steroid-associated ONFH can progressively break down the underlying bone of the hip joint and thus induce severe premature osteoarthritis of the hip, which would further cause physical disability in these SARS survivors [4].…”

“…Not all patients with steroid-associated ONFH have undergone operative treatments [4,6]. Disappointingly, a meta-analysis published in 2019 had concluded that postmarketing drugs, including enoxaparin, statins, bisphosphonates, iloprost and acetylsalicylic acid, were not recommendable for this disease [7].…”

“…In China, quite a few ONFH patients are undergoing pharmacological treatments, especially treatment by traditional Chinese medicine (TCM) [4,6,10]. In 2012, "Chinese Experts' Consensus on the Diagnosis and Treatment of Osteonecrosis of the Femoral Head in Adults (2012)" recommended Chinese medicine as one of the pharmacological treatments for ONFH [11].…”