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.

Expression of HSPA8 in Nucleus Pulposus of Lumbar Intervertebral Disc and Its Effect on Degree of Degeneration.

INTRODUCTION: This study aimed to investigate the expression of a 70-kDa heat shock protein [heat shock 70-kDa protein 8 (HSPA8)/heat shock protein 70 (Hsc70)] in human degenerative lumbar intervertebral discs and its relationship with the degree of degeneration of human intervertebral discs. METHODS: A total of 72 cases of lumbar intervertebral disc nucleus pulposus tissues were collected. Among these, 18 cases of nucleus pulposus tissue were assigned to the control group, while 54 cases of nucleus pulposus tissues were assigned to the experimental group. According to the preoperative MRI, cases in the experimental group were further divided into three groups: protrusion group (n = 18), extrusion group (n = 18), and sequestration group (n = 18). Western blot was performed to determine the relative expression of HSPA8 in the nucleus pulposus in each group. Hematoxylin and eosin staining was performed to determine the number of nucleus pulposus cells, morphological differences, and cell densities of the degenerated intervertebral discs and normal intervertebral discs. Immunohistochemistry was performed to determine the expression of HSPA8 in nucleus pulposus tissues in each group. RESULTS: Hematoxylin and eosin staining results: There were significant differences in cell morphology and number between the control group and the experimental group. Furthermore, there were significant differences in cell density (F = 936.80, P < 0.01). Immunohistochemistry results: HSPA8 was expressed in lumbar intervertebral disc nucleus pulposus tissues, and its expression of gradually decreased with the severity of the disease, and the differences were significant (F = 2110.43, P < 0.01). Western blot results: The expression of HSPA8 in human degenerative nucleus pulposus tissues gradually decreased, and the differences were significant (F = 1841.72, P < 0.01). CONCLUSION: HSPA8 is stably expressed in human intervertebral disc nucleus pulposus tissues, and its expression is associated with the degree of intervertebral disc degeneration.

The research of transgenic human nucleus pulposus cell transplantation in the treatment of lumbar disc degeneration.

The present study determines whether the in vivo injection of TGFß1 and CTGF mediated by AAV2 to transfect nucleus pulposus cells in degenerative lumbar discs can reverse the biological effects of rhesus lumbar disc degeneration. A total of 42 lumbar discs obtained from six rhesus monkeys were classified into three groups: experimental group, control group, and blank group. Degenerative lumbar discs were respectively injected with double gene-transfected human nucleus pulposus cells using minimally invasive techniques. Immumohistochemical staining, RT-PCR, and western blot were performed to observe the biological effects of double gene-transfected human nucleus pulposus cells in degenerative lumbar discs on rhesus lumbar disc degeneration. At 4, 8, and 12 weeks after the transplantation of nucleus pulposus cells, the expression levels of TGF-ß1, CTGF, proteoglycan mRNA, and type-II collagen were detected by RT-PCR. The values of immumohistochemical staining and RT-PCR in the experimental group increased at 8 weeks, decreased with time at 12 weeks, and remained greater than the values in the control group, and the differences were statistically significant (P < .05). The western blot revealed that the values in the experimental group decreased with time, but remained greater than those in the PBS control group and blank control group, and the differences were statistically significant (P < .05). The double gene-transfection of human nucleus pulposus cells in degenerative lumbar discs mediated by rAAV2 can be continuously expressed in vivo after transplantation in lumbar discs of rhesus monkeys, and promotes the synthesis of proteoglycan and type II collagen, achieving the treatment purpose.