OBJECTIVE: To investigate the effect of teriparatide on the differentiation of MC3T3-E1 cells in high-glucose microenvironment and explore the possible mechanism. METHODS: MC3T3-E1 cells cultured in normal glucose or high-glucose (25 mmol/L) medium were treated with 10 nmol/L teriparatide with or without co-treatment with H-89 (a PKA inhibitor). CCK-8 assay was used to detect the changes in cell proliferation, and cAMP content in the cells was determined with ELISA. Alkaline phosphatase (ALP) activity and mineralized nodules in the cells were detected using ALP kit and Alizarin red staining, respectively. The changes in cell morphology were detected by cytoskeleton staining. Real-time PCR was used to detect the mRNA expressions of PKA, CREB, RUNX2 and Osx in the treated cells. RESULTS: The treatments did not result in significant changes in proliferation of MC3T3-E1 cells (P > 0.05). Compared with the cells in routine culture, the cells treated with teriparatide showed significantly increased cAMP levels (P < 0.05) with enhanced ALP activity and increased area of mineralized nodules (P < 0.05). Teriparatide treatment also resulted in more distinct visualization of the cytoskeleton in the cells and obviously up-regulated the mRNA expressions of PKA, CREB, RUNX2 and Osx (P < 0.05). The opposite changes were observed in cells cultured in high glucose. In cells exposed to high glucose, treatment with teriparatide significantly increased cAMP levels (P < 0.05), ALP activity and the area of mineralized nodules (P < 0.05) and enhanced the clarity of the cytoskeleton and mRNA expressions of PKA, CREB, RUNX2 and Osx; the effects of teriparatide was strongly antagonized by co-treatment with H-89 (P < 0.05). CONCLUSION Teriparatide can promote osteoblast differentiation of MC3T3-E1 cells in high-glucose microenvironment possibly by activating the cAMP/PKA/CREB signaling pathway.
Cell Differentiation ; Core Binding Factor Alpha 1 Subunit ; Glucose/pharmacology* ; Osteoblasts/drug effects* ; RNA, Messenger ; Signal Transduction ; Teriparatide ; Animals ; Mice ; Cell Line

Teriparatide has been known to aid in the treatment of osteoporosis but its use in the management of fracture disorders is poorly documented. This review aims to show that teriparatide administration may improve the healing process in fractures that fail to unite after sustaining trauma. A total of 22 reported cases have been identifi ed from 2009 to 2017. Teriparatide doses were given in a median duration of 5.6 months with a median time to complete union of 8.5 months. This review systematically summarizes all clinical case reports of non-union treated with teriparatide for us to gain insight into its off-label use.
Teriparatide

Anorexia nervosa (AN) affects 2.9 million people, many of whom experience bone loss and increased fracture risk. In this article, we review data on the underlying pathophysiology of AN-related osteoporosis and possible approaches to disease management. Available research suggests that low body weight and decreased gonadal function are the strongest predictors of bone loss and fractures in patients with AN. Additionally, other metabolic disturbances have been linked to bone loss, including growth hormone resistance, low leptin concentrations, and hypercortisolemia, but those correlations are less consistent and lack evidence of causality. In terms of treatment of AN-related bone disease, weight gain has the most robust impact on bone mineral density (BMD). Restoration of gonadal function seems to augment this effect and may independently improve BMD. Bisphosphonates, insulin-like growth factor 1 supplementation, and teriparatide may also be reasonable considerations, however need long-term efficacy and safety data.
Anorexia Nervosa ; Anorexia ; Body Weight ; Bone Density ; Bone Diseases ; Diphosphonates ; Disease Management ; Feeding and Eating Disorders ; Gonads ; Growth Hormone ; Humans ; Leptin ; Osteoporosis ; Teriparatide ; Weight Gain

Globally, the elderly population is increasing rapidly, which means that the number of deformity correction operations for elderly spine deformity patient has increased. On the other hand, for aged patients with deformity correction operation, preoperative considerations to reduce the complications and predict a good clinical outcome are not completely understood. First, medical comorbidity needs to be evaluated preoperatively with the Cumulative Illness Rating Scale for Geriatrics or the Charlson Comorbidity Index scores. Medical comorbidities are associated with the postoperative complication rate. Managing these comorbidities preoperatively decreases the complications after a spine deformity correction operation. Second, bone densitometry need to be checked for osteoporosis. Many surgical techniques have been introduced to prevent the complications associated with posterior instrumentation for osteoporosis patients. The preoperative use of an osteogenesis inducing agent
Aged ; Comorbidity ; Compensation and Redress ; Congenital Abnormalities ; Densitometry ; Geriatrics ; Hand ; Humans ; Lower Extremity ; Osteogenesis ; Osteoporosis ; Pelvis ; Postoperative Complications ; Posture ; Spine ; Teriparatide

OBJECTIVE: Osteoporosis is one of the most common causes of vertebral compression fractures (VCFs). Teriparatide, a recombinant human parathyroid hormone, is the first anabolic agent for the treatment of osteoporosis. The aim of this study was to determine whether 3 months of teriparatide could be effective for patients with osteoporotic VCF at the thoracolumbar spine. METHODS: We reviewed 25 patients with thoracolumbar osteoporotic compression fractures between July 2012 and October 2016 who could be followed up for more than 1 year. Patients were divided into 2 groups depending on the use of teriparatide: 14 patients received teriparatide through subcutaneous injection (group I) and 11 patients did not receive teriparatide (group II). Demographic data, bone mineral density, hospitalization period, changes in the visual analogue scale (VAS) score, body mass index, and medical history such as smoking, alcohol, diabetes, and steroid usage were reviewed. Radiographs were also reviewed to evaluate vertebral body compression percentages and kyphotic angles. RESULTS: Overall changes of VAS score between injury and follow-up were statistically improved in both groups at 2 to 3 weeks post-injury. However, difference in VAS improvement at a specific time between the 2 groups was not statistically significant. Overall kyphotic angle and compression percentage between injury and follow-up time were increased in group II than those in group I, although the difference between the 2 groups was not statistically significant. CONCLUSION: Three-month of teriparatide did not show protective effects on progression of fractured vertebral body collapse or kyphotic changes in patients with osteoporosis.
Body Mass Index ; Bone Density ; Follow-Up Studies ; Fractures, Compression ; Hospitalization ; Humans ; Injections, Subcutaneous ; Osteoporosis ; Osteoporotic Fractures ; Parathyroid Hormone ; Smoke ; Smoking ; Spine ; Teriparatide ; Thoracic Vertebrae ; Treatment Outcome

OBJECTIVES: The impact of patient background factors on changes in bone mineral density (BMD) and bone metabolic markers after treatment with once-weekly teriparatide (W-TPTD) has not been fully elucidated. To clarify the impact, I performed stratified analysis in addition to the efficacy and safety assessments to analyze treatment data with W-TPTD. METHODS: The primary endpoint of the efficacy was the rate of change of the lumbar spine BMD at 18 months after treatment. In the exploratory analysis, bone metabolic markers at baseline were used to divide the patients into 3 groups, by the first tertile and the second tertile. The rate of change in the lumbar spine/femoral neck BMD and bone metabolic markers in each group were analyzed by stratification. RESULTS: The rate of change in the lumbar spine BMD at 18 months was 9.0%, which represented a significant increase. The rate of change in the lumbar spine/femoral neck BMD in each group classified into tertiles by their baseline bone metabolic markers significantly increased, regardless of the type of bone metabolic markers and baseline value. For markers, all groups remained within the range of reference values at 18 months after treatment. CONCLUSIONS: I demonstrated that W-TPTD significantly increased the BMD of the lumbar spine and femur, regardless of baseline values of the bone metabolic markers. In addition, W-TPTD was able to normalize bone metabolic markers. I considered that W-TPTD would be useful, independent of bone metabolic markers in patients, as an agent to improve BMD, and be a useful option for the treatment of osteoporosis.
Bone Density ; Femur ; Humans ; Neck ; Osteoporosis ; Reference Values ; Spine ; Teriparatide ; Treatment Outcome

OBJECTIVES: To reassess the safety and efficacy of once-weekly teriparatide 56.5 mg in osteoporosis patients with a high fracture risk. METHODS: This postmarketing observational study was conducted at 72 weeks according to the package insert. Of the 3573 Japanese osteoporosis patients in the safety analysis set, 91.80% were women, the mean age was 78.1 years, and 69.89% had a history of prevalent fragility fractures, indicating that a high proportion of patients at high risk of fracture were enrolled. RESULTS: Persistence with weekly teriparatide treatment was 59.36%, and 38.95% at 24 and 72 weeks, respectively. Adverse drug reactions (ADRs) were reported in 898 patients (25.13%), and serious ADRs were reported in 26 patients (0.73%). The most frequent ADRs were nausea, vomiting, and headache. The cumulative incidence of new vertebral fractures 72 weeks after the start of treatment was 3.31%. Increases in the bone mineral density were observed in the lumbar spine, femoral neck, and proximal femur. The serum levels of the bone formation markers, procollagen type I N-terminal propeptide and bone-type alkaline phosphatase, increased slightly at 24 weeks and then decreased to baseline levels. At 24 and 72 weeks, the bone resorption markers, serum cross-linked N-terminal telopeptide of type I collagen and urinary cross-linked N-terminal telopeptide of type I collagen, were the same as or slightly lower than at baseline. Visual analogue scale scores for low back pain also decreased. CONCLUSIONS: The present results showed that once-weekly teriparatide may also be useful for osteoporosis patients with a high risk of fracture.
Alkaline Phosphatase ; Asian Continental Ancestry Group ; Biomarkers ; Bone Density ; Bone Resorption ; Collagen Type I ; Drug-Related Side Effects and Adverse Reactions ; Female ; Femur ; Femur Neck ; Headache ; Humans ; Incidence ; Low Back Pain ; Nausea ; Observational Study ; Osteogenesis ; Osteoporosis ; Product Labeling ; Spine ; Teriparatide ; Vomiting

No abstract available.
Teriparatide

STUDY DESIGN: Retrospective case review. PURPOSE: To assess the incidence and effect of teriparatide (TP) on subsequent vertebral fractures following a long-instrumented fusion surgery for osteoporotic vertebral fractures (OVFs). OVERVIEW OF LITERATURE: TP treatment may be a useful strategy for patients with OVFs treated with a long-instrumented surgery. METHODS: Overall, 47 patients who underwent long-instrumented fusion surgery (≥3 levels) for OVFs with neurological deficits between 2010 and 2013 were enrolled. The mean age of the subjects was 76 years; the study population comprised 20 males and 27 females. The mean follow-up duration was 23 months. The average of fused vertebrae was 4.9. TP was used for 19 patients who comprised the TP group. The incidence of subsequent VFs was estimated with Kaplan–Meier analyses and compared between the TP and non-TP groups using the log-rank test. Risk factors were evaluated using a Cox proportional hazards model. RESULTS: A total of 38% (18/47 cases) of the subjects were identified with subsequent VFs. There were no significant differences in the age, sex, fused levels, presence of prevalent fractures, and correction loss of the two groups. The occurrence of subsequent VFs was lower in the TP group than in the non-TP group (16% vs. 54%, p=0.014). The log-rank test revealed that the TP treatment significantly reduced the risk of subsequent VFs (p=0.048). A Cox proportional hazards model revealed that preoperative TP treatment is only a protective factor of subsequent VFs after instrumented fusion surgery for OVFs (hazard ratio, 0.281; p=0.047). CONCLUSIONS: In this retrospective study, pre- and postoperative TP treatment significantly reduced the incidence of subsequent VFs after instrumented fusion surgery for OVFs. A prospective randomized study is warranted to determine the efficacy of TP treatments.
Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Osteoporosis ; Proportional Hazards Models ; Prospective Studies ; Protective Factors ; Retrospective Studies ; Risk Factors ; Spine ; Teriparatide

OBJECTIVE: To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts. METHODS: Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; =6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of β-catenin and RANKL protein in the cells were analyzed. RESULTS: The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice ( < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice ( < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of β-catenin and increased the expression of RANKL as compared with TPTD treatment alone. CONCLUSIONS Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.
Animals ; Bone Density ; Bone Density Conservation Agents ; administration & dosage ; pharmacology ; Bone Resorption ; drug therapy ; Bone and Bones ; drug effects ; metabolism ; Female ; Growth Plate ; drug effects ; Mice ; Mice, Inbred C57BL ; Osteoclasts ; drug effects ; Ovariectomy ; RANK Ligand ; metabolism ; Teriparatide ; administration & dosage ; pharmacology ; beta Catenin ; metabolism