Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis.

BACKGROUND: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. METHODS: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. RESULTS: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and ß-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. CONCLUSION: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

Percutaneous Endoscopic Interlaminar Discectomy with Modified Sensation-Motion Separation Anesthesia for Beginning Surgeons in the Treatment of L5-S1 Disc Herniation.

PURPOSE: To compare the clinical effects of local anesthesia (LA), general anesthesia (GA) and modified sensation-motion separation anesthesia (MA) in percutaneous endoscopic interlaminar discectomy (PEID) in the treatment of L5/S1 lumbar disc herniation (LDH) for the purpose of guiding junior surgeons. METHODS: Eighty-four patients with L5/S1 LDH underwent PEID using three anesthesia methods. Patients in the LA (26), GA (29) and MA (29) groups received a follow-up examination retrospectively. The general parameters, preparation and anesthesia duration, operative duration, recovery time, incidence of complications, ambulation time, length of hospital stay, incidence of severe complications, and reoperation rate were compared, and clinical outcomes were analyzed using a visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Short-Form Health Survey 36 (SF-36). RESULTS: MA demonstrated obvious advantages over the other two methods with respect to operative duration and resulted in a better intraoperative experience than LA. The patients in the MA group required less time in bed postoperatively and shorter hospital stays than those in the GA group. The mean postoperative VAS, ODI and SF-36 scores were significantly better than the preoperative scores in all groups (P<0.05), but no significant differences in these scores were found among the three groups (P>0.05). Three cases (3/29) of nervous disorder occurred in the GA group. Two patients (one in the GA group (1/29) and one in the LA (1/26) group) underwent revision surgery, with a total recurrence rate of 2.4% (2/84). CONCLUSION: Due to its high safety and good tolerance by patients, MA is a suitable method for spinal surgeons who are inexperienced with PEID in the treatment of L5/S1 disc herniation.

Myocardin­related transcription factor A nuclear translocation contributes to mechanical overload­induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration.

Previous studies have reported that the Ras homolog family member A (RhoA)/myocardin­related transcription factor A (MRTF­A) nuclear translocation axis positively regulates fibrogenesis induced by mechanical forces in various organ systems. The aim of the present study was to determine whether this signaling pathway was involved in the pathogenesis of nucleus pulposus (NP) fibrosis induced by mechanical overload during the progression of intervertebral disc degeneration (IVDD) and to confirm the alleviating effect of an MRTF­A inhibitor in the treatment of IVDD. NP cells (NPCs) were cultured on substrates of different stiffness (2.9 and 41.7 KPa), which mimicked normal and overloaded microenvironments, and were treated with an inhibitor of MRTF­A nuclear import, CCG­1423. In addition, bipedal rats were established by clipping the forelimbs of rats at 1 month and gradually elevating the feeding trough, and in order to establish a long­term overload­induced model of IVDD, and their intervertebral discs were injected with CCG­1423 in situ. Cell viability was determined by Cell Counting Kit­8 assay, and protein expression was determined by western blotting, immunofluorescence and immunohistochemical staining. The results demonstrated that the viability of NPCs was not affected by the application of force or the inhibitor. In NPCs cultured on stiff matrices, MRTF­A was mostly localized in the nucleus, and the expression levels of fibrotic proteins, including type I collagen, connective tissue growth factor and α­smooth muscle cell actin, were upregulated compared with those in NPCs cultured on soft matrices. The levels of these proteins were reduced by CCG­1423 treatment. In rats, 6 months of upright posture activated MRTF­A nuclear­cytoplasmic trafficking and fibrogenesis in the NP and induced IVDD; these effects were alleviated by CCG­1423 treatment. In conclusion, the results of the present study demonstrated that the RhoA/MRTF­A translocation pathway may promote mechanical overload­induced fibrogenic activity in NP tissue and partially elucidated the molecular mechanisms underlying the occurrence of IVDD.

Risk Factors for Recurrent L4-5 Disc Herniation After Percutaneous Endoscopic Transforaminal Discectomy: A Retrospective Analysis of 654 Cases.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) is an increasingly applied minimally invasive procedure that has several advantages in the treatment of lumbar disc herniation (LDH). However, recurrent LDH (rLDH) has become a concerning postoperative complication. It remains difficult to establish a consensus and draw reliable conclusions regarding the risk factors for rLDH. PURPOSE: This retrospective study aimed to investigate the risk factors associated with rLDH at the L4-5 level after percutaneous endoscopic transforaminal discectomy (PETD). METHODS: A total of 654 patients who underwent the PETD procedure at the L4-5 level from October 2013 to January 2020 were divided into a recurrence (R) group (n=46) and a nonrecurrence (N) group (n=608). Demographic and clinical data and imaging parameters were collected and analyzed using univariate and multiple regression analyses. RESULTS: The current study found a 7% rate of rLDH at the L4/5 level after successful PETD. Univariate analysis showed that older age, high BMI, diabetes mellitus history, smoking, large physical load intensity, moderate disc degeneration, small muscle-disc ratio (M/D), more fat infiltration, large sagittal range of motion (sROM), scoliosis, small disc height index (DHI), small intervertebral space angle (ISA), and small lumbar lordosis (LL) were potential risk factors (P < 0.10) for LDH recurrence after PETD at the L4-5 level. Multivariate analysis suggested that high BMI, large physical load intensity, moderate disc degeneration, small M/D, more fat infiltration, large sROM, small ISA, and small LL were independent significant risk factors for recurrence of LDH after PETD. CONCLUSION: Consideration of disc degeneration, M/D, fat infiltration of the paravertebral muscles, sROM, ISA, LL, BMI, and physical load intensity prior to surgical intervention may contribute to the prevention of rLDH following PETD and lead to a more satisfactory operative outcome and the development of a reasonable rehabilitation program after discharge.