Teriparatide Group Research Articles

Role of teriparatide (rh PTH) in fracture healing of osteoporotic patient

Introduction: Osteoporosis a disease where decreased bone strength increases the risk of a fracture. It is the most common reason for fracture among the elderly. Osteoporosis, an imbalance between bone resorption and bone formation. The diagnosis of osteoporosis can be made using conventional radiography and by measuring the bone mineral density. Osteoporosis is diagnosed when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young reference. Teriparatide, a recombinant form of parathyroid hormone (identical to a portion of human parathyroid hormone (PTH)), intermittent use activates osteoblasts more than osteoclasts, which leads to an overall increase in bone turnover. Teriparatide is the only anabolic agent (i.e., bone growing) indicated for use in postmenopausal women with osteoporosis at a high risk for fracture or with a history of osteoporotic fracture, patients with multiple risk factors for fracture. It has been FDA-approved since 2002. Materials and Methods: Over duration of october 2016 to march 2018, 60 patients who have fracture with osteoporosis admitted in S.N. Medical College, Agra. Patient suspected to have osteoporosis based on conventional radiography. Selected patients in the study undergone confirmation of osteoporosis by dual energy absorptiometry and those who are below 2.5 standard deviation are kept in study. Patients fitting into inclusion criteria would form the study group. Data collected by interviews, observation of clinical and radiological findings. 60 patients divided in two groups as cases and controls. Cases are subjected to teriparatide therapy and controls given placebo. Results: Bone formation marker alkaline phosphatase were 150% above baseline after 8 weeks in the teriparatide-treated patient. At 8 weeks, approximately 91.037% in the teriparatide group showed improved healing of osteoporotic fracture compared to 57.14% in the placebo group. Conclusion: Our findings suggest that teriparatide provide selective advantages to fracture healing or functional recovery in the management of osteoporotic fractures. Teriparatide effective in accelerating and increasing the rate of fracture healing. However, more randomized controlled trials are needed to evaluate with certainty the impacts of Teriparatideosteoanabolic role in fracture healing to decide on incorporate this drug as a standard option for conservative management of osteoporotic fracture.

Abaloparatide Effects on Cortical Volumetric BMD and Estimated Strength Indices of Hip Subregions by 3D-DXA in Women With Postmenopausal Osteoporosis

In ACTIVE, abaloparatide increased areal BMD (aBMD) of the hip and femoral neck vs teriparatide and placebo in women with osteoporosis. Previously, 3D-processing of dual X-ray absorptiometry (DXA) scans of a subgroup of ACTIVE subjects showed similar increases in trabecular volumetric BMD (Tb.vBMD) and greater increases in cortical vBMD (Ct.vBMD) of the total hip with abaloparatide vs teriparatide. The current analyses from this subgroup describe 2D- and 3D-DXA data for hip subregions. Randomly selected subjects from ACTIVE (n = 250/treatment group) who received 18 mo of placebo, abaloparatide 80 µg, or open-label teriparatide 20 µg by daily subcutaneous injection underwent hip DXA at baseline, and mo 6 and 18 of treatment. Areal BMD of the femoral neck, trochanter, and femoral shaft was determined using standard 2D-DXA and 3D-SHAPER software to retrospectively evaluate changes from baseline in volumetric parameters of these 3 hip subregions, including trabecular and cortical segmentation. Changes in biomechanical parameters cross-sectional moment of inertia (CSMI), section modulus (Z), and buckling ratio were also evaluated. Femoral neck, trochanter, and shaft aBMD increased in the abaloparatide and teriparatide groups at mo 6 and 18 vs placebo, with greater increases for abaloparatide vs teriparatide at the femoral neck at mo 6 and the shaft at mo 6 and 18. All 3 subregions showed similar significant increases in Tb.vBMD with abaloparatide and teriparatide vs placebo, whereas Ct.vBMD of all 3 subregions showed greater increases after 18 mo of abaloparatide vs teriparatide. Biomechanical parameters improved in all subregions with abaloparatide and teriparatide vs placebo, with greater improvements in CSMI and Z of the femoral neck and lower shaft after 6 and 18 mo of abaloparatide vs teriparatide. Differential femoral neck and shaft Ct.vBMD responses may explain the greater increases in CSMI and Z of those subregions with abaloparatide vs teriparatide.

EFFICACY OF TERIPARATIDE IN COMMINUTED FRACTURE HEALING IN LOWER LIMB: A RETROSPECTIVE STUDY

Objective: The objective of the study was to show the efficacy of teriparatide in comminuted fracture healing and improvement in overall functional recovery. Methods: A total of 30 subjects who suffered from comminuted fractures of lower limb were selected. Subjects were categorized into two groups: Group A (n=15) contained individuals with teriparatide administration and Group B (n=15) contained individuals who were not administered teriparatide. 20 mg of teriparatide was injected subcutaneously for a period of 3 months. Patients were followed up ay durations of 4, 8, and 12 weeks. Obtained data were entered into Microsoft Excel Worksheets and descriptive analysis was performed. Chi-square test was used to analyze all obtained data. Results: Among Group A patients, the fracture healing rates were found to be significantly earlier with comparison to control group (Group B). Conclusion: Teriparatide was observed to be effective in comminuted fracture healing and has demonstrated good clinical outcome.

Zoledronic acid and teriparatide have a complementary therapeutic effect on aseptic loosening in a rabbit model

BackgroundRevisions are mainly caused by wear debris-induced aseptic loosening. How to effectively suppress debris-induced periprosthetic osteolysis has become an urgent problem. Both zoledronic acid and teriparatide can increase the bone mass around prostheses and increase the stability of prostheses. A hypothesis was proposed: the combination of the two drugs may have a better treatment effect than the use of either drug alone.MethodsWe created a rabbit model to study the effect and mechanism of the combination of zoledronic acid and teriparatide in the treatment of aseptic loosening. Thirty-two adult male New Zealand white rabbits were selected and treated with TKA surgery, and a titanium rod prosthesis coated evenly with micrometre-sized titanium debris was implanted into the right femoral medullary cavity. All rabbits were randomized into four groups (control group = 8, zoledronic acid group = 8, teriparatide group = 8, and zoledronic acid + teriparatide group = 8). All the animals were sacrificed in the 12th week, and X-ray analyses, H&E staining, Goldner-Masson trichrome staining, von Kossa staining, and RT-PCR and Western blotting of the mRNA and protein of OCN, OPG, RANKL and TRAP5b in the interface membrane tissues around the prostheses were immediately carried out.ResultsThe results shown that both zoledronic acid and teriparatide could inhibit debris-induced peri-prosthetic osteolysis and promote new bone formation. Zoledronic acid was more capable of inhibiting osteoclast activation and peri-prosthetic osteolysis, while teriparatide was more capable of promoting osteoblast function and peri-prosthetic bone integration.ConclusionThis research confirmed that the combination of zoledronic acid and teriparatide could prevent and treat aseptic loosening of the prosthesis more effectively. However, the safety of this combination and the feasibility of long-term application have not been ensured, and the clinical application requires further experiments and clinical research support.

A randomized, controlled trial of once-weekly teriparatide injection versus alendronate in patients at high risk of osteoporotic fracture: primary results of the Japanese Osteoporosis Intervention Trial-05

SummaryIn this randomized, controlled trial, treatment with once-weekly subcutaneous injection of teriparatide for 72 weeks was found to be associated with a significant reduction in the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture.IntroductionTo determine whether the anti-fracture efficacy of teriparatide is superior to that of alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed.MethodsJapanese women aged at least 75 years were eligible for the study if they had primary osteoporosis and were at high risk of fracture. Patients were randomly assigned in a 1:1 ratio to receive sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint was the incidence of morphometric vertebral fractures at 72 weeks (at the end of teriparatide treatment).ResultsBetween October 2014 and December 2017, 1011 patients (505 in the teriparatide group and 506 in the alendronate group) were enrolled. Of these, 778 patients (351 and 427, respectively) were included in the primary analysis. The incidence of morphometric vertebral fractures was significantly lower in the teriparatide group (56 per 419.9 person-years, annual incidence rate 0.1334) than in the alendronate group (96 per 553.6 person-years, annual incidence rate 0.1734), with a rate ratio of 0.78 (95% confidence interval 0.61 to 0.99, P = 0.04). In both groups, adverse events were most frequently reported in the following system organ classes: infections and infestations, gastrointestinal disorders, and musculoskeletal and connective tissue disorders.ConclusionOnce-weekly subcutaneous injection of teriparatide significantly reduced the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture.Trial registrationjRCTs031180235 and UMIN000015573, March 12, 2019

Effect of Teriparatide on pain relief, and quality of life in postmenopausal females with osteoporotic vertebral compression fractures, a retrospective cohort study.

Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures. In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 µg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd months, the 6th months and 1 year after treatment. Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration. In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.

Effects of Teriparatide on Treatment Outcomes in Osteoporotic Hip and Pelvic Bone Fractures: Meta-analysis and Systematic Review of Randomized Controlled Trials.

The primary objective of this study was to evaluate randomized controlled trials (RCTs) that have reported the effects of teriparatide on bone-healing in osteoporotic hip and pelvic bone fractures to determine the efficacy of teriparatide in lowering the rate of treatment failure. A total of 2,809 studies were identified using a comprehensive literature search (MEDLINE [n=1,061], Embase [n=1,395], and Cochrane Library n=353]). Five RCTs were included in the final analysis. Treatment failure rates at the last follow-up of osteoporotic hip and pelvic bone fractures between the teriparatide and control groups was the primary outcome. Treatment failure was defined as non-union, varus collapse of the proximal fragment, perforation of the lag screw, and any revision in cases due to mechanical failure of the implant during the follow-up period. The number of treatment failures in the teriparatide and placebo groups were 11.0% (n=20 out of 181) and 17.6% (n=36 out of 205), respectively. Although the rate of treatment failure in the teriparatide group was lower than that in the control group, this difference was not significant (odds ratio, 0.81 [95% confidence interval, 0.42–1.53]; P=0.16; I2=42%). This meta-analysis did not identify any significant differences in the rate of treatment failure between the teriparatide and control groups at final follow-up. Based on these results, we believe that there is a lack of evidence to confirm efficacy of teriparatide in reducing treatment failures in osteoporotic hip and pelvic bone fractures.

Efficacy of once-weekly teriparatide in patients with glucocorticoid-induced osteoporosis: the TOWER-GO study.

Bisphosphonates are the standard treatment for glucocorticoid-induced osteoporosis (GIOP) with teriparatide being another option. While daily teriparatide has been shown to be effective in increasing bone mineral density (BMD), the efficacy of once-weekly teriparatide (56.5µg) has not yet been evaluated. The TOWER-GO study, a 72-week, multicenter, open-label, randomized controlled trial, was conducted in patients with GIOP to compare the effects of once-weekly teriparatide and once-weekly alendronate 35mg on BMD. Patients (N = 180) with GIOP for whom drug treatment was indicated according to the 2004 guidelines in Japan were randomized to receive once-weekly teriparatide (n = 89) or once-weekly alendronate (n = 91). The primary endpoint was the non-inferiority of percentage change in lumbar spine BMD at final follow-up. The secondary endpoints were the percentage change in BMD from baseline, incidence of bone fractures, and changes in bone turnover markers. While the non-inferiority of teriparatide to alendronate was not confirmed, BMD increased significantly from baseline with teriparatide and alendronate by 5.09% and 4.04%, respectively (both p < 0.05), at 72weeks. The incidence of vertebral and non-vertebral fractures was similar in both groups. Bone formation markers increased in the teriparatide group and decreased in the alendronate group. The non-inferiority of once-weekly teriparatide versus once-weekly alendronate in BMD change at 72weeks was not shown, but the increase in bone formation markers over time and the increase of BMD in GIOP patients treated with once-weekly teriparatide were confirmed.

Use of teriparatide prior to lumbar fusion surgery lowers two-year complications for patients with poor bone health

IntroductionPoor bone health can create challenges in management which are amplified for patients undergoing spinal fusion. Although previously shown to improve outcomes postoperatively, the impact of preoperative teriparatide use on long-term complications remains unclear. In this study, we investigated the complication rates within two years of surgery for osteoporotic and osteopenic patients using teriparatide prior to lumbar fusion procedures. MethodsPatients with poor bone health undergoing any lumbar fusion surgery at a single institution between 2008 and 2018 were identified and subsequently divided into two groups as teriparatide and non-teriparatide group. Baseline demographics, patient and surgery related factors, and two-year complications were collected through a retrospective chart review. Multivariable logistic regression was performed to evaluate the association between teriparatide usage and development of any related postoperative complication. ResultsA total of 42 and 114 patients were identified for the teriparatide and non-teriparatide groups, respectively. The median age (IQR) for the teriparatide group was 62 years (55.8−68.8), while the non-teriparatide group had a median (IQR) age of 70 years (64−75.8). Overall, there were no statistically significant differences in terms of individual complications between the groups. However, on adjusted regression analysis, teriparatide use was associated with significantly lower odds of related complications for lumbar fusion patients (p = 0.049). ConclusionTeriparatide use prior to lumbar fusion procedures resulted in reduced rate of osteoporosis-related complications within two years postoperatively. Results suggest improved outcomes might be seen in patients with osteopenia and osteoporosis when pre-treating with teriparatide.

234. Cost-effectiveness analysis of teriparatide therapy for the prevention of proximal junctional kyphosis/failure and subsequent revision after adult spinal deformity surgery

BACKGROUND CONTEXT Recent studies have shown teriparatide therapy reduces the risk of proximal junctional kyphosis/failure (PJK/PJF) and subsequent revision after corrective surgery for adult spinal deformity (ASD). However, teriparatide usually costs more than other anti-osteoporotic treatments and its cost effectiveness for the prevention of these unfavorable sequelae is unclear. PURPOSE The aim of this study is to investigate the cost effectiveness of preoperative teriparatide therapy for ASD patients utilizing a Markov model of ASD corrective surgery. STUDY DESIGN/SETTING An economic decision-analysis based on a Markov model simulation. PATIENT SAMPLE A thorectical cohort of patients with adult spinal deformity patients who undergo corrective surgery. OUTCOME MEASURES Cost/QALY and the rates of patients who successfully achieved fusion without any correction loss due to PJK/PJF. METHODS A Markov model of ASD surgery was created incorporating the incidences of PJK/PJF and revision rates due to PJK/PJF in the surgically treated ASD patient with or without 12-month teriparatide treatment, revision rates for non-PJK causes, recurrence rates of PJK/PJF, postoperative mortality, and pre-/postoperative quality-adjusted life-years (QALYs), obtained from previously published literature. The effectiveness was measured in cost/QALY and the rates of patients who successfully achieved fusion without any correction loss due to PJK/PJF in each group. RESULTS The Markov model simulation showed that the 10-year cumulative cost was higher in the teriparatide group ($131,000 vs $83,000). The percentage of patients without correction loss at 10 years after surgery was also higher in the teriparatide group (86.9% vs 76.7%). The 10-year average QALYs of each group were 0.59 in the no teriparatide group and 0.61 in the teriparatide group. The cost-effectiveness of 12-month teriparatide therapy measured in cost/QALY was $213,000/QALY, which was almost twice as high as the commonly used cost-effectiveness threshold ($100,000/QALY). Teriparatide therapy can be considered as cost-effective only if teriparatide therapy less than 6 months is as effective as 12 months of treatment for PJK/PJF prevention, or teriparatide is administrated only for high-risk patients whose 24-month PJK/PJF incidence rate exceeds approximately 40% without teriparatide ($94000/QALY). CONCLUSIONS The results of our Markov model simulation suggest that teriparatide therapy is associated with lower correction loss, but is not a cost-effective option if it is routinely administered in all ASD patients regardless of bone status. Careful selection of high-risk patients for teriparatide therapy is warranted as a more cost-effective measure. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Effects of Teriparatide versus Salmon Calcitonin Therapy for the Treatment of Osteoporosis in Asia: A Meta-analysis of Randomized Controlled Trials

The objective of this meta-analysis was to compare the efficacy and safety of teriparatide versus salmon calcitonin for the treatment of osteoporosis in Asian patients and to investigate whether the results of global studies could be applicable to Asian patients. PubMed, OVID, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE up to December 2018 were searched. Eligible randomized controlled trials (RCTs) that compared teriparatide versus salmon calcitonin in Asian osteoporosis population were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data synthesis, and Cochrane Collaboration software Review Manager 5.3 was used to analyze the pooled data. Three RCTs involving 529 patients were included (mean age 68.7 yr; 93.4% females; mean follow-up 6 months); outcome measures included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine; bone markers and adverse events. We found that the period of 6-months of teriparatide treatment was helpful for the improvement of the BMD of lumbar vertebra, however, the improvement of BMD was not significant in the femoral neck and total hip joint. There was a positive correlation between bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCN) and the response of Asian patients to subcutaneous injection of 20 micrograms per day of teriparatide. The proportion of the occurrence of adverse effects was more obvious in the teriparatide group compared with salmon calcitonin, but there was no significant difference. Results suggested that the use of teriparatide could improve the lumbar BMD by shortterm (six months) application in Asian osteoporosis patients, which is beneficial to the patients who cannot tolerate adverse events of long-term treatment. The BSAP and OCN bone markers could be useful to monitor the responses of Asian osteoporosis patients to teriparatide treatment. Finally, both of teriparatide and salmon calcitonin were well tolerated by Asian patients.

Effects of denosumab versus teriparatide in glucocorticoid-induced osteoporosis patients with prior bisphosphonate treatment

IntroductionOsteoporosis is one of the serious adverse effects associated with glucocorticoid therapy. Although bisphosphonates have been used for glucocorticoid-induced osteoporosis (GIO), some patients have shown an inadequate response. In such cases, denosumab or teriparatide are used. However, there is no consensus on which of these two drugs is superior. We prospectively compared denosumab's and teriparatide's effects on the bone mineral density (BMD) in GIO patients with prior bisphosphonate treatment. Materials and methodsAfter receiving oral bisphosphonates for ≥2 years, GIO patients with low T-score BMD (<−2.5) were switched from bisphosphonates to denosumab (n = 20) or daily teriparatide (n = 21). We measured the BMD (lumbar spine, femoral neck, and total hip) in both groups every 6 months for 24 months. ResultsAt 24 months of treatment, the lumbar spine BMD increased significantly from baseline in both the denosumab and teriparatide groups (baseline vs. denosumab and teriparatide; 5.9 ± 5.6%, P < 0.001 and 7.9 ± 5.4%, P < 0.001). A significant increase in femoral neck BMD from baseline occurred only in the teriparatide group (6.6 ± 10.8%, P < 0.05); denosumab (1.5 ± 5.0%). No significant changes occurred in the total hip BMD from baseline in either group (−0.1 ± 5.6% and 3.3 ± 7.5%, respectively). There was no significant difference between the denosumab and teriparatide groups at 24 months in lumbar spine and femoral neck BMD, but was significantly higher in the teriparatide group at 12 months (P < 0.01 and P < 0.05 in the lumbar spine and femoral neck, respectively). ConclusionTeriparatide might have some advantages over denosumab and be a good alternative for treating GIO patients with prior bisphosphonate treatment.

Effect of bisphosphonates or teriparatide on mechanical complications after posterior instrumented fusion for osteoporotic vertebral fracture: a multi-center retrospective study

BackgroundThe optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures.MethodsRetrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced.ResultsA total of 159 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.1% vs 58.2%, p = 0.045). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP.ConclusionsThe overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients. The use of TP was effective to reduce postoperative complications for OVF patients treated with posterior fusion.

Effects of abaloparatide and teriparatide on bone resorption and bone formation in female mice

Intermittent administration of PTH type 1 receptor (PTH1R) agonists increases bone remodeling, with greater stimulation of bone formation relative to bone resorption causing net gains in bone mass. This pharmacodynamic feature underlies the bone-building effects of teriparatide and abaloparatide, the only PTH1R agonists approved to reduce osteoporotic fracture risk in postmenopausal women. This study in 8-week-old female mice compared bone resorption and formation responses to these agents delivered at the same 10 μg/kg dose, and a 40 μg/kg abaloparatide dose was also included to reflect its 4-fold higher approved clinical dose. Peptides or vehicle were administered by daily supra-calvarial subcutaneous injection for 12 days, and local (calvarial) and systemic (L5 vertebral and tibial) responses were evaluated by histomorphometry. Terminal bone histomorphometry data indicated that calvarial resorption cavities were similar in both abaloparatide groups versus vehicle controls, whereas the teriparatide group had more calvarial resorption cavities compared with the vehicle or abaloparatide 40 μg/kg groups. The bone resorption marker serum CTX was significantly lower in the abaloparatide 40 μg/kg group and similar in the other two active treatment groups compared with vehicle controls. Both peptides increased trabecular bone formation rate (BFR) in L5 and proximal tibia versus vehicle, and L5 BFR was higher with abaloparatide 40 μg/kg versus teriparatide. At the tibial diaphysis, periosteal BFR was higher with abaloparatide 40 μg/kg versus vehicle or teriparatide, and endocortical BFR was higher with teriparatide but not with abaloparatide 10 or 40 μg/kg versus vehicle. Few differences in structural or microarchitectural bone parameters were observed with this brief duration of treatment. In summary, calvarial bone resorption cavity counts were higher in the teriparatide group versus the vehicle and abaloparatide 40 μg/kg groups, and the abaloparatide 40 μg/kg group had lower serum CTX versus vehicle. L5 and tibial trabecular bone formation indices were higher in all three active treatment groups versus vehicle. The abaloparatide 40 μg/kg group had higher L5 trabecular BFR and tibial periosteal BFR versus teriparatide, whereas tibial endocortical BFR was higher with teriparatide but not abaloparatide. Together, these findings in female mice indicate that an improved balance of bone formation versus bone resorption is established shortly after initiating treatment with abaloparatide.

Management of medication-related osteonecrosis of jaw: Comparison between icariin and teriparatide in a rat model.

The aim of this study is to compare the effects of icariin and teriparatide on the treatment of medication-related osteonecrosis of the jaw (MRONJ) using a rat model. Fifty rats undergoing ovariectomy were randomly assigned to control group (n=10) and the MRONJ model group (n=40). Zoledronic acid (0.2mg/kg) and dexamethasone (2mg/kg) were injected into rats in the model group for 8weeks while saline was applied in control group, then all rats underwent tooth extraction and bone defect. Eightweeks later, rats diagnosed with MRONJ (n=33) were randomly distributed to icariin (n=11), teriparatide (n=11), and the untreated (n=11) group, and rats received daily 150mg/kg icariin, 20µg/kg teriparatide, and no intervention, respectively, for 8weeks. Then, mandibulars were dissected for later examination. Rats diagnosed with MRONJ (33/40) demonstrated significantly larger area of soft tissue wound and necrotic bone with higher ratio of empty bone lacuna. Area of soft tissue wound and ratio of empty bone lacuna were significantly decreased in the icariin group compared with the untreated group, while teriparatide group revealed significantly higher ratio of receptor activator of NF-kB ligand (RANKL)-positive osteocytes, smaller area of necrotic bone and lower ratio of empty lacuna. The two agents were related to higher expression of BMP-2 in osteocytes but were not statistically significant. Icariin benefits MRONJ in terms of the area of soft tissue wound and ratio of empty lacuna. Teriparatide activates expression of RANKL and reduces the area of bone necrosis and ratio of empty lacuna in a MRONJ lesion. The data suggest possible healing improvement in patients with MRONJ and further studies to prove the efficacy of icariin.

Effects of Injected Antiosteoporotic Medication Versus Oral Bisphosphonates on Rates of Repeated Vertebroplasty or Kyphoplasty

PurposeVertebral compression fractures can recur within a few years after percutaneous vertebroplasty (PVP) or kyphoplasty. MethodsWe conducted a population-based study using data from the Taiwan National Health Insurance Research Database to investigate the efficacy of various antiosteoporotic treatments in reducing the prevalence rate of repeated PVP or kyphoplasty in patients hospitalized from January 1, 1997, to December 31, 2004. We included patients with vertebral compression fractures after PVP or kyphoplasty who received oral bisphosphonates (OB group; n = 6141) or injected drug therapies (injection group; n = 4308). FindingsThe incidence rate of repeated PVP or kyphoplasty was significantly lower in the I/Z/D (denosumab monotherapy or ibandronate or zoledronate with or without denosumab) group than in the OB group (crude subdistribution hazard ratio [sHR], 0.79; 95% CI, 0.70–0.90; P < 0.05; adjusted sHR, 0.77; 95% CI, 0.68–0.87; P < 0.0001). The analysis revealed a significantly lower incidence rate of repeated PVP or kyphoplasty in the I/Z group compared with that in the OB group (crude sHR, 0.82; 95% CI, 0.72–0.94; P = 0.0038; adjusted sHR, 0.80; 95% CI, 0.70–0.91; P = 0.0011). The denosumab group also exhibited a significantly lower incidence rate of repeated PVP or kyphoplasty than did the OB group (crude sHR, 0.61; 95% CI, 0.46–0.80; P = 0.0005; adjusted sHR, 0.58; 95% CI, 0.44–0.77; P = 0.0001). Although the teriparatide group had higher fracture frequency than did the OB group, the analysis revealed no significant difference between the OB and teriparatide groups with respect to the incidence rate of repeated PVP or kyphoplasty (adjusted sHR, 1.08; 95% CI, 0.92–1.26; P = 0. 3747). ImplicationsInjected antiosteoporotic medication was associated with lower rates of repeated vertebroplasty and kyphoplasty than was OB application.

Efficacy of teriparatide compared with risedronate on FRAX\xae-defined major osteoporotic fractures: results of the VERO clinical trial

SummaryFRAX® calculates the 10-year probability of major osteoporotic fractures (MOF), which are considered to have a greater clinical impact than other fractures. Our results suggest that, in postmenopausal women with severe osteoporosis, those treated with teriparatide had a 60% lower risk of FRAX®-defined MOF compared with those treated with risedronate.IntroductionThe VERO trial was an active-controlled fracture endpoint clinical trial that enrolled postmenopausal women with severe osteoporosis. After 24 months, a 52% reduction in the hazard ratio (HR) of clinical fractures was reported in patients randomized to teriparatide compared with risedronate. We examined fracture results restricted to FRAX®-defined major osteoporotic fractures (MOF), which include clinical vertebral, hip, humerus, and forearm fractures.MethodsIn total, 1360 postmenopausal women (mean age 72.1 years) were randomized to receive subcutaneous daily teriparatide (20 μg) or oral weekly risedronate (35 mg). Patient cumulative incidence of ≥ 1 FRAX®-defined MOF and of all clinical fractures were estimated by Kaplan-Meier analyses, and the comparison between treatments was based on the stratified log-rank test. Additionally, an extended Cox model was used to estimate HRs at different time points. Incidence fracture rates were estimated at each 6-month interval.ResultsAfter 24 months, 16 (2.6%) patients in the teriparatide group had ≥ 1 low trauma FRAX®-defined MOF compared with 40 patients (6.4%) in the risedronate group (HR 0.40; 95% CI 0.23–0.68; p = 0.001). Clinical vertebral and radius fractures were the most frequent FRAX®-defined MOF sites. The largest difference in incidence rates of both FRAX®-defined MOF and all clinical fractures between treatments occurred during the 6- to 12-month period. There was a statistically significant reduction in fractures between groups as early as 7 months for both categories of clinical fractures analyzed.ConclusionIn postmenopausal women with severe osteoporosis, treatment with teriparatide was more efficacious than risedronate, with a 60% lower risk of FRAX®-defined MOF during the 24-month treatment period. Fracture risk was statistically significantly reduced at 7 months of treatment.Clinical trial informationClinicalTrials.gov Identifier: NCT01709110EudraCT Number: 2012-000123-41

Teriparatide Associated with Fewer Refractures and Higher Body Heights of Cemented Vertebrae after Vertebroplasty: A Matched Cohort Study

Refracture of cemented vertebrae occurs commonly after vertebroplasty (VP) for osteoporotic vertebral compression fracture (OVCF). It can result in severe pain or neurological deficit, but no preventive medication is available. Owing to the bone anabolic benefits of teriparatide (TP), this study was aimed to compare the outcomes of cemented vertebrae with TP to those without TP. Patients who received VP for OVCF with at least 1 year follow-up were included. The anterior body height (ABH) and middle body height (MBH) and kyphotic angle (KA) were measured before VP and 1 week and at least 1 year after VP. Refracture was defined as a 15% decrease in ABH or MBH and 8° decrease in KA compared with those at postoperative 1 week. The clinical outcomes were evaluated. 35 VP procedures in 21 patients treated with TP (TP group), and, matched to that, 29 out of 133 patients treated with VP alone (VP group) were included. One year after VP, ABH and MBH were significantly greater, except KA, in the TP group (VP group vs. TP group: KA − 4.97° ± 12.1 vs. −2.85° ± 12.21°, p = 0.462, ABH 1.56 ± 0.48 cm vs. 1.84 ± 0.56 cm, p = 0.027, MBH 1.49 ± 0.39 cm vs. 1.73 ± 0.41 cm, p = 0.017). The refracture rates of KA, ABH, and MBH were significantly lower in the TP group (VP group vs. TP group: KA 42.11% vs.8.57%, p < 0.001; ABH 76.32% vs. 28.57%, p < 0.0001; MBH 76.32% vs. 28.57%, p < 0.0001). In single-level subgroup comparison, TP was associated with better improvement of pain VAS and better radiological outcomes. TP was associated with higher BHs and fewer refractures than VP alone, with comparable clinical outcomes 1 year after VP. TP may be associated with better improvement of pain VAS in those with single-level VP procedure. Higher BH was due to the better maintenance effect of TP.

Comparison between teriparatide and bisphosphonates for improving bone mineral density in postmenopausal osteoporosis patients: A meta-analysis.

Background:We performed a systematic review and meta-analysis of the efficacy and safety of teriparatide and bisphosphonates in managing postmenopausal osteoporosis.Methods:PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure were searched for relevant randomized controlled trials that were published before April 2018 and compared teriparatide and bisphosphonates in treating postmenopausal osteoporosis. Stata 12.0 was used for the meta-analysis. The pooled risk ratio (RR) or weighted mean difference and 95% confidence interval (CI) were calculated using a fixed effects or random effects meta-analysis.Results:A total of 14 randomized controlled trials were included in this meta-analysis. The teriparatide group was associated with a lower total occurrence of vertebral fractures (RR = 0.55, 95% CI: 0.40–0.77; P = .001) and nonvertebral fractures (RR = 0.65, 95% CI: 0.46–0.90; P = .009) than the bisphosphonate group. Moreover, compared with the bisphosphonate group, the teriparatide group had improved bone mineral density at the lumbar spine and femoral neck at the final follow-up (P < .05). There was no significant difference between the teriparatide and bisphosphonate groups in terms of complications (RR = 1.05, 95% CI: 0.90, 1.22, P = .516).Conclusions:Teriparatide significantly reduced the occurrence of vertebral and nonvertebral fractures in osteoporosis patients. More studies should focus on the quality of life of patients using these 2 drugs.

Histological assessment of the effects of teriparatide therapy on mandibular fracture healing: A preclinical study

ObjectiveThis study was performed to evaluate the effects of teriparatide therapy on mandibular fracture healing in a rat model. Subjects and methodsA unilateral mandibular fracture, 5 mm posterior to the last molar tooth, was surgically created in 120 rats. Half of the animals received a daily subcutaneous injection of 2 μg/kg teriparatide while the control rats received normal saline, starting from the day of surgery until sacrifice. Twenty rats from each group were sacrificed on postoperative days 10, 20, and 30. The healing process was evaluated histologically and scored using a grading system (ranging from 1 to 10). ResultsOn day 10 the fracture gaps of the control and teriparatide groups were mainly filled with fibrous tissue and new trabecular bone, respectively. On day 20 a large amount of new trabecular bone and some areas of fibrocartilaginous tissue were seen in the fracture gaps of the control rats. In the teriparatide group the fracture area was entirely filled with trabecular bone, which in some areas had been replaced by mature bone. On day 30 the fracture gaps of the control group were entirely bridged by new trabecular bone, while in the teriparatide group they was predominantly filled with mature bone. At all three time-points the mean healing scores for the teriparatide group (6.20 ± 0.70, 8.50 ± 0.69, and 9.85 ± 0.37, respectively) were significantly higher (p < 0.001) than for the control group (4.90 ± 0.55, 7.15 ± 0.59, and 8.90 ± 0.64, respectively). ConclusionBased on the results of this study, teriparatide should be tested in humans in order to establish whether comparable results can be achieved.