ABSTRACT
OBJECTIVE: To investigate the therapeutic effects of PERK activator CCT020312 (CCT) on inflammation-mediated osteoporosis (IMO) in ovariectomized rats. METHODS: Rats were divided into Sham, IMO, IMO + 1 mg/kg CCT and IMO + 2 mg/kg CCT groups. IMO models were constructed by bilateral ovariectomy (OVX) on 1st day followed by injection with magnesium silicate (Talc) on the 59th day. Sham rats did not undergo OVX surgery and were injected with saline instead of Talc. From 60th to 79th day, rats were treated with DMSO (vehicle control) in the Sham and IMO groups, and 1 or 2 mg/kg CCT020312 in treatment groups. Osteopontin (OPN), osteocalcin (OCN), tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type I collagen (CTX-I), and pro-inflammatory factors were measured on the 80th day. ProdigyDEXA was used to evaluate bone mineral density and content (BMD/BMC). Bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number (Tb.N), and trabecular separation (Tb.Sp) was assessed using 3D micro-CT scanner. RESULTS: CCT up-regulated Conn.D, BV/TV, and Tb.N, but down-regulated Tb.Sp in IMO rats. Besides, the declined femoral BMD and BMC in IMO rats were elevated after CCT treatment. Besides, IMO rats represented declined OPN and OCN, as well as increased TRAP, CTX-I, and pro-inflammatory factors, whereas those in the treatment groups were ameliorated regarding these indexes, with 2 mg/kg CCT showing better effect. CONCLUSION: PERK activator CCT020312 can be served as a new therapeutic option for the protection against bone loss in the OVX rat model associated with inflammation probably by manipulating inflammatory factors.
Subject(s)
Bone Density/drug effects , Bone and Bones/drug effects , Enzyme Activators/pharmacology , Ovariectomy , eIF-2 Kinase , Absorptiometry, Photon , Animals , Bone and Bones/diagnostic imaging , Bone and Bones/metabolism , Cancellous Bone/diagnostic imaging , Cancellous Bone/drug effects , Collagen Type I/drug effects , Collagen Type I/metabolism , Femur/diagnostic imaging , Femur/drug effects , Femur/metabolism , Humans , Imaging, Three-Dimensional , Inflammation/metabolism , Organ Size , Osteocalcin/drug effects , Osteocalcin/metabolism , Osteopontin/drug effects , Osteopontin/metabolism , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/metabolism , Peptide Fragments/drug effects , Peptide Fragments/metabolism , Rats , Tartrate-Resistant Acid Phosphatase/drug effects , Tartrate-Resistant Acid Phosphatase/metabolism , X-Ray MicrotomographyABSTRACT
BACKGROUND: We explored the clinical effect of one-stage posterior debridement and bone grafting with internal fixation for the treatment of monosegmental thoracolumbar tuberculosis (TB). METHODS: The data from 90 patients with thoracolumbar TB, who had undergone one-stage posterior debridement and bone grafting with internal fixation, were retrospectively reviewed. Data on the operative time, blood loss, length of hospital stay, erythrocyte sedimentation rate, C-reactive protein, improvement of neurological function, visual analog scale score, vertebral Cobb angle, bone healing, and complications were collected. RESULTS: A total of 88 patients were finally included in the present retrospective study, included 42 men and 46 women. The mean patient age was 45.4 ± 12.3 years (range, 27-70), and the mean duration of disease until treatment was 11 ± 4.5 months (range, 3-19). The mean operative time was 167.0 minutes (range, 130-210), and the mean blood loss was 767.4 mL (range, 500-1150). At the final follow-up examination, the correction in the Cobb angle was 19°, the visual analog scale score had decreased to 3 ± 1.72, the neurologic deficits using the Frankel grade had improved, and the erythrocyte sedimentation rate and C-reactive protein level had returned to normal levels. CONCLUSION: One-stage posterior debridement and bone grafting with internal fixation might be a better choice for treating patients with monosegment thoracolumbar TB.
