Postmenopausal osteoporosis (PMOP) is a condition in women caused by estrogen deficiency, characterized by reduced bone mass and increased fracture risk. Fatty acid-binding protein 4 (FABP4), a lipid-binding protein involved in metabolism and inflammation, has emerged as a key regulator in metabolic disorders and bone resorption; however, its direct role in PMOP remains unclear. Here, we show that serum FABP4 levels in PMOP patients negatively correlate with bone mineral density, a trend also observed in ovariectomized mice. FABP4 promotes osteoclast formation and bone resorption without affecting osteoblast differentiation. The FABP4 inhibitor BMS309403 suppresses osteoclast differentiation by modulating calcium signaling and inhibiting the Ca²⁺-Calcineurin-NFATc1 pathway. Oral BMS309403 increases bone mineral density in ovariectomized mice, though less effectively than alendronate. Notably, bone-targeted delivery of BMS309403 achieves comparable efficacy to alendronate. In this work, we demonstrate that FABP4 is a critical mediator in PMOP and that its inhibition offers a promising therapeutic strategy.

Retrospective clinical study. To retrospectively evaluate the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and progressive congenital scoliosis (CS) associated with split spinal cord malformation (SSCM). For severe and rigid spinal deformity, spinal osteotomies are often advocated for correcting the deformity. However, the safety and efficacy of one-stage spinal osteotomy in the treatment of severe and rigid CS with SSCM have been unclear thus far. Patients were treated by one-stage spinal osteotomy between September 2007 and June 2011 in our hospital. The clinical records were reviewed for demographic and radiographical data, operative time, intraoperative blood loss, blood transfusion, perioperative complications, and functional outcomes. There were 18 females and 11 males with an average age of 15.5 ± 3.6 years (range, 12-28 yr). Spinal cord was longitudinally split by a bony spur in 11 patients (type I SSCM) and by a fibrous band in 18 patients (type II SSCM). Patients were observed for a minimum of 24 months after initial surgical treatment with an average follow-up of 43.0 ± 17.1 months (range 24-68 mo) from September 2007 to June 2013. The mean operative time and average blood loss of type ISSCM was significantly greater than those of type II SSCM (P < 0.05). The major curve was corrected from an average of 97.2°± 17.8° to 35.7°± 15.9°, a mean correction rate of 64.3% ± 11.0%. The average loss of correction at final follow-up was 2.9% for major curves. The overall complication rate was 24.1%, including transient neurological deterioration in 3 patients, cerebrospinal fluid leakage in 2 patients, urinary tract infection in 1 patient and pleural rupture in 1 patient. Relative to multistage corrective surgery, one-stage spinal osteotomy is effective for the correction of severe CS and SSCM without increasing the rate of surgical complications. However, surgical treatment of type I SSCM does require more operating time and blood loss. 4.

Neural stem cell (NSC) transplantation is a promising strategy for replacing lost neurons following spinal cord injury. However, the survival and differentiation of transplanted NSCs is limited, possibly owing to the neurotoxic inflammatory microenvironment. Because of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages, we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase (AR), a key enzyme in the polyol pathway of glucose metabolism, would provide a more beneficial microenvironment for NSC survival and differentiation. Here, we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries. M2 macrophages promoted the differentiation of NSCs into neurons in vitro. Transplantation of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional recovery. Our findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.