Huo Xue Tong Luo capsule, a vasoactive herbal formula prevents progression of asymptomatic osteonecrosis of femoral head: A prospective study

Abstract

Background/objective: A prospective cohort study aimed to evaluate the clinical efficacy of a specific vasoactive herbal formula, Huo Xue Tong Luo capsule (HXTL capsule), for the treatment of patients with asymptomatic osteonecrosis of femoral head (ONFH).

Methods: We evaluated a clinical trial of 55 patients (59 hips) with asymptomatic ONFH (no joint collapse) evaluated by Steinberg staging system and necrosis range classification criteria. Then, they were given HXTL capsule under specific protocol. Among them, 39 males and 16 females with an average age of 36.4 ± 10.1 years were followed up for an average of 4.38 years during treatment. The aggravation of clinical and imaging results was assessed by initial pain and joint collapse. The clinical and imaging outcomes of these patients were compared with those of a historical control group from the literature under critical inclusion criteria.

Results: At the latest follow-up, initial pain occurred in five of 59 (8.5%) hips of patients taking HXTL capsule compared with 31 of 81 (38.3%) controls (p < 0.001), and joint collapse occurred in 13 of 59 (22.0%) hips of patients taking HXTL capsule compared with 26 of 81 (32.1%) controls (p < 0.001). There was no association between joint collapse and multiple key factors of ONFH. Only the location of type C2 necrotic lesions (hazard ratio, 4.12; 95% confidence interval, 2.64-18.91) and the extent of large necrotic lesions (hazard ratio, 3.39; 95% confidence interval, 1.43-16.21) predicted joint collapse.

Conclusion: As an agent formulated by vasoactive herbals, HXTL capsule with specific protocol is an effective medicine for relieving hip pain and preventing joint collapse in patients with asymptomatic ONFH.

The translational potential of this article: The translation potential of this prospective cohort study is that the initially officially approved clinical indication for HXTL capsule for treatment of ONFH is due to its possible effect of revascularization on angiogenesis of necrosis. It is has been now proven to be effective for a new clinical application.

Keywords: Clinical progression; Femoral head; HXTL capsule; Osteonecrosis; Radiographic evaluation.

Fig. 1

Patients taking a Huo Xue Tong Luo capsule (HXTL capsule; treatment group) and historical controls (control group) with any presenting Steinberg stage osteonecrosis of the femoral head (ONFH) after more than 4 years of follow-up. (A) The treatment group exhibited a significantly lower percentage of cases with clinical pain progression of ONFH than the control group. (B) The treatment group exhibited a significantly lower percentage of cases with radiographic progression of ONFH than the control group.

Fig. 2

Kaplan–Meier survivorship curve. (A) The cumulative rates of survival (with 95% confidence intervals) are 96.6% at 4 years, 83.5% at 6 years, 72.5% at 8 years and 60.2% at 9 years with collapse of the femoral head as the endpoint. (B) Survival rates according to initial Steinberg stages of osteonecrosis. There were no differences (p = 0.607, log-rank test) in survival among hips classified at different Steinberg stages. (C) Survival rates according to the initial extent of the osteonecrosis as determined by magnetic resonance imaging (MRI) using the method of Steinberg et al. (Steinberg et al., 1995). The time to collapse was different (p = 0.000, log-rank test) among the three groups. (D) Survival rates according to the location of osteonecrosis. The time to collapse was different (p = 0.000, log-rank test) among the three groups.

Figure 3

A 34-year-old man who received steroid therapy for nephrotic syndrome. (A) Frog-leg lateral radiographs and anteroposterior radiographs show bilateral asymptomatic hips with stage I disease at his initial diagnosis. (B) After taking Chinese medicine for two years, the patient was free from symptoms and had no collapse of the femoral heads bilaterally on frog-leg lateral radiographs and anteroposterior radiographs four and a half years later. (C) Six and a half years later, the patient was free from symptoms and had no radiographic progression of the left femoral head, but collapse of the right femoral head was seen on a frog-leg lateral radiograph, not on an anteroposterior radiograph. (D) MRI image of the suffered hip obtained at his initial diagnosis. (E) Until eight years later, the patient was free from symptoms and had good function. MRI = magnetic resonance imaging.

Figure 4

A 38-year-old man who received steroid therapy for brainstem encephalitis. (A–C) Anteroposterior radiograph and frog-leg lateral radiograph showing a right asymptomatic hip with stage II disease at his initial diagnosis. The patient took Chinese medicine for two years, and radiographs taken seven years and ten years later showed no progression to collapse of the femoral head. (D) MRI image of the suffered hip obtained at his initial diagnosis. (E) The patient was free from symptoms and had good function. MRI = magnetic resonance imaging.