Doxycycline as a Potential MMP-1 Inhibitor for the Treatment of Spondylitis Tuberculosis: A Study in Rabbit Model.

Background: Tuberculosis (TB) of the spine is a highly disruptive disease, especially in underdeveloped and developing countries. This condition requires standard TB treatment for 9-18 months, which increases patient risk of drug-resistant TB. Consequently, this raises the concern of adopting additional therapies to shorten the treatment duration, improve the efficacy of anti-TB drugs, and further decrease damage in the affected tissues and organs. Matrix metalloproteinase- (MMP-) 1 is a key regulator of the destruction of the extracellular matrix and associated proteins and is a new potential target for TB treatment research. In the present study, we investigated the effects of doxycycline as an MMP-1 inhibitor in patients with spondylitis TB. Methods: Seventy-two New Zealand white rabbits with spondylitis TB were divided into 12 different groups based on incubation period (2, 4, 6, and 8 weeks) and doxycycline administration (without, 1 mg/kg body weight (BW), and 5 mg/kg BW). We observed the course of infection through the blood concentration changes and immunohistochemical examination of MMP-1, in addition to BTA staining, culture, polymerase chain reaction (PCR), and histopathological examination. Results: Treatment with once daily 5 mg/kg BW doxycycline significantly improved the blood MMP-1 level (p < 0.05) compared with the placebo and 1 mg/kg BW doxycycline. A significantly reduced ongoing infection and a higher healing rate were demonstrated in rabbits with a higher doxycycline dose through BTA staining, culture, PCR, and histopathology. Various degrees of vertebral endplates, vertebral body, and intervertebral disc destruction were observed in 32 rabbits with positive histopathological findings, in addition to positive inflammatory cell infiltration, characterized by numerous lymphocytes, macrophages, and epithelial cells, as well as abundant granulation tissue and necrotic substances proximal to the inoculated vertebral area. Bone and intervertebral disc destructions were more apparent in the untreated rabbits. Conclusion: Our study demonstrated the potential of doxycycline as an adjunctive treatment in spondylitis TB. However, limitations remain regarding the differences in the pathogenesis and virulence of Mycobacterium tuberculosis between rabbit and human systems, sample size, and the dose-dependent effect of doxycycline. Further studies are needed to address these issues.

Prevalence of proximal tibia vara in Indonesian population with knee osteoarthritis.

Background: Proximal tibia vara has drawn interest since the concept of constitutional varus was introduced. Proximal tibia vara is a condition where the knee varus tilt the tibia condyle medially and shift the tibial articular surface medially. This condition affects medial proximal tibial angle measurements and the placement of the tibial implant in knee replacement surgery. Thus, it challenged the neutral knee arthroplasty alignment target because some people may present a proximal tibia vara. This study assesses the prevalence of the proximal tibia vara and the correlation to knee osteoarthritis grade. Methods: This retrospective study was carried out from January 2021 to June 2021. Eighty-five limbs were included with the following inclusion criteria: knee osteoarthritis patients who received a long view lower extremity radiograph. The exclusions criteria were (1) patients who had undergone arthroplasty and lower extremity surgery before and (2) valgus knee deformity. The outcomes in this study were HKAA, MAD, TAD, MPTA, PTRP, LDFA, and PTS. Intraclass correlation (ICC) using two-way mixed was used to assess the reproducibility of the radiographic parameters. Multiple logistic regression was used to evaluate the correlation between knee osteoarthritis grade and radiographs parameters (MAD and TAD). Result: A total 85 limbs from 52 patients were assessed in this study. Proximal tibia vara was found in 18 knees (21%.). The logistic regression was performed to assess the correlation between the severity of the knee osteoarthritis and radiographic parameters (MAD, TAD, LDFA, and PTS) with an overall p-value < 0.001 and pseudo-R2 = 0.29. Conclusion: A significant portion of patients with knee osteoarthritis have proximal tibia vara, and it is a pre-existing condition. Since the pre-existing proximal tibia vara affects preoperative measurements, a long-standing lower extremity x-ray is recommended to be obtained as part of knee replacement preparation.