Teriparatide Administration Research Articles

Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan

BackgroundTherapeutic strategies for patients with medication-related osteonecrosis of the jaw (MRONJ) remain controversial. The aim of the present study was to clarify the effectiveness and safety of teriparatide therapy in Japanese MRONJ patients based on a large number of case series with a multicenter retrospective analysis. Patients and methodsBetween January 2012 and December 2016, 29 patients who were diagnosed with MRONJ at 10 hospitals were treated with teriparatide. The medical records of these patients were retrospectively reviewed to assess the efficacy and safety of teriparatide therapy for MRONJ patients. ResultsAdverse events occurred in 17.2% of patients (5/29). One patient developed severe arthralgia and discontinued teriparatide therapy after 12 days, while others continued the treatment. Among 29 patients, the median period of administration of teriparatide was 14.0 months (range, 0.3–26 months), and treatment outcomes were evaluated as effective in 75.9% of patients with complete resolution in 65.5%. Among patients treated with oral bisphosphonates (BPs), 83.3% were effectively treated with teriparatide and 40% with intravenous BPs. The oral administration of BPs was associated with successful treatment outcomes with teriparatide (p = 0.062). ConclusionsTeriparatide therapy has potential as an effective treatment option for MRONJ.

Bone Mineral Density Response With Denosumab in Combination With Standard or High-Dose Teriparatide: The DATA-HD RCT.

In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide. In the current analysis, we compare the individual rates of aBMD response between the treatment groups. Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-μg daily (SD) or 40-μg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months' total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared. Postmenopausal women with osteoporosis completing all study visits (n = 60). aBMD (dual x-ray absorptiometry). At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively). Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.

Effects of teriparatide on fusion rates in patients undergoing complex foot and ankle arthrodesis

BackgroundHere, we determined whether teriparatide treatment would increase fusion rates after foot and ankle arthrodesis by comparing treatment results between patients with high-risk factors for nonunion who received teriparatide against those who did not. MethodsWe retrospectively reviewed 66 consecutive patients who underwent foot and ankle arthrodesis. The inclusion criterion was the presence of at least one of the following risk factors for nonunion after previous foot and ankle arthrodesis: deformity, bone defects, avascular necrosis, and nonunion. Sixteen patients were finally enrolled and divided into 2 groups: 8 patients received teriparatide treatment after fusion surgery (PTH group), and 8 patients did not (control group). ResultsThe fusion rate was significantly greater in the PTH group than in the control group (100% vs 50%). Four patients in the control group developed nonunion, 3 of whom underwent revision fusion; however, all patients received the teriparatide treatment after revision surgery and subsequently achieved union. No significant differences in demographics, fusion sites, and complication rates were found. ConclusionThough the sample size was small, the current study suggests that teriparatide administration may improve fusion rates in patients with high-risk factors for nonunion after foot and ankle arthrodesis.

Factors affecting continuation of weekly teriparatide administration in rural areas.

Although teriparatide plays an important role in the treatment of patients with severe osteoporosis, it is meaningless if patients cannot continue. There have been few reports of studies evaluating factors affecting the continuation rate of weekly teriparatide; moreover, no study has investigated the relationship between the distance to travel to the hospital and continuation rate. Therefore, we examined the continuation rate of weekly teriparatide and factors that affect this rate. This retrospective study included 73 patients who were administered weekly teriparatide in a rural hospital. Patient information, including the age, sex, distance between the hospital and home, family structure, place of introduction, reason for the start of teriparatide administration, past osteoporosis treatment and fracture, side effects, and period of teriparatide continuation, was collected. We examined factors influencing weekly teriparatide continuation. The continuation rate of weekly teriparatide was 22.7%. The Kaplan-Meier curves for the two groups regarding the place of introduction and side effects showed significant differences (P = 0.0158 and P = 0.0309, respectively). In the multivariate analyses to investigate factors associated with teriparatide continuation, an older age, starting administration while hospitalized, and side effects were identified as risk factors negatively influencing continuation (P = 0.0280, P = 0.0222, and P = 0.0095, respectively). On the other hand, the number of family members and distance between our hospital and home did not affect teriparatide continuation. An older age, starting administration while hospitalized, and side effects were identified as risk factors negatively influencing teriparatide continuation.

Combination denosumab and high dose teriparatide for postmenopausal osteoporosis (DATA-HD): a randomised, controlled phase 4 trial

In the Denosumab and Teriparatide Administration (DATA) study, we showed that denosumab fully inhibits teriparatide-induced bone resorption while allowing for continued teriparatide-induced bone formation, resulting in larger increases in hip and spine bone mineral density (BMD) than with either drug alone. We aimed to assess whether administration of denosumab with high dose teriparatide would stimulate larger increases in bone mass than those observed in the DATA study. DATA-HD was an open-label, randomised, controlled phase 4 trial done at Massachusetts General Hospital. Eligible women were postmenopausal women (at least 36 months since last menses or since hysterectomy with a follicle-stimulating hormone concentration of ≥40 U/L) with osteoporosis. Participants were randomly assigned (1:1) to receive teriparatide 20 μg (standard dose) or 40 μg (high dose) daily via subcutaneous injection for 9 months. At 3 months, both groups were started on denosumab 60 mg every 6 months via subcutaneous injection for 12 months. Areal BMD (aBMD) was measured at 0, 3, 9, and 15 months. Treatment was given open label, but outcome assessors were masked. The primary endpoint was percentage change from baseline in spine areal BMD (aBMD) at 15 months. Women who completed at least one study visit after baseline were included in the modified intention-to-treat analysis. Safety was assessed in all randomly assigned participants. This study is registered with ClinicalTrials.gov, number NCT02176382. Between Oct 15, 2014, and June 10, 2016, 269 women were assessed for eligibility. 76 participants were randomly assigned to 20 μg teriparatide (n=39) or 40 μg teriparatide (n=37), of whom 69 completed at least one post-baseline visit. At 15 months, mean spine aBMD had increased to a significantly greater extent in the 40 μg group (17·5% [SD 6·0] increase) than the 20 μg group (9·5% [3·2]; difference 8·1%, 95% CI 5·5 to 10·6, p<0·0001). Mean femoral neck aBMD had also increased to a greater extent in the 40 μg group (6·8% [SD 4·1] increase) than the 20 μg group (4·3% [3·7]; difference 2·5%, 0·5 to 4·5, p=0·04), as did mean total hip aBMD (40 μg group, 6·1% [3·4] increase; 20 μg group, 3·9% [2·9] increase; difference 2·2%, 0·6 to 3·8, p<0·0001). 30 (77%) of 39 participants in the 20 μg group and 29 (78%) of 37 participants in the 40 μg group had an adverse event, and seven (18%) and two (5%) patients had serious adverse events. The most frequent adverse events were joint pain (15 [38%]), muscle cramp (15 [38%]), and fatigue (12 [31%]) in the 20 μg group group and fatigue (14 [38%]), nausea (16 [43%]), and joint pain (17 [46%]) in the 40 μg group. No deaths were reported. Combined treatment with teriparatide 40 μg and denosumab increases spine and hip BMD more than standard combination therapy. This large and rapid increase in bone mass suggest that this high dose regimen might provide a method of restoring skeletal integrity in patients with osteoporosis. National Institutes of Health and the Dart Foundation.

Standard Versus Cyclic Teriparatide and Denosumab Treatment for Osteoporosis: A Randomized Trial.

In the absence of an intervening antiresorptive agent, cyclic administration of teriparatide does not increase bone mineral density (BMD) more than standard daily therapy. Because denosumab is a potent antiresorptive agent with a rapid off-effect, we hypothesized that it might be the optimal agent to help maximize bone gains with cyclic teriparatide. In this 3-year protocol, 70 postmenopausal women with osteoporosis were randomized to 18 months of teriparatide followed by 18 months of denosumab (standard) or three separate 12-month cycles of 6 months of teriparatide followed by 6 months of denosumab (cyclic). BMD (dual-energy X-ray absorptiometry [DXA]) measurements of lumbar spine (LS), total hip (TH), femoral neck (FN), and 1/3 radius (RAD) were performed every 6 months and total body bone mineral (TBBM) at 18 and 36 months. Baseline descriptive characteristics did not differ between groups except for a minimal difference in LS BMD but not T-score (mean age 65 years, mean LS T-score - 2.7). In the standard group, BMD increments at 36 months were: LS 16%, TH 4%, FN 3%, and TBBM 4.8% (all p < 0.001 versus baseline). In the cyclic group, 36-month BMD increments were similar: LS 12%, TH 4%, FN 4%, and TBBM 4.1% (all p < 0.001 versus baseline). At 36 months, the LS BMD increase with standard was slightly larger than with cyclic (p = 0.04), but at 18 months, in the cyclic group, there was no decline in RAD or TBBM (p = 0.007 and < 0.001, respectively, versus standard). Although the cyclic regimen did not improve BMD compared with standard at 36 months, there appeared to be a benefit at 18 months, especially in the highly cortical skeletal sites. This could be clinically relevant in patients at high imminent risk of fracture, particularly at nonvertebral sites. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Impact of Weekly Teriparatide on the Bone and Mineral Metabolism in Hemodialysis Patients With Relatively Low Serum Parathyroid Hormone: A Pilot Study.

Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH.

Effects of Weekly Teriparatide Administration for Vertebral Stability and Bony Union in Patients with Acute Osteoporotic Vertebral Fractures.

Study DesignAn open-label, non-randomized prospective study.PurposeTeriparatide (TPTD) is known to be an antiosteoporotic agent that may accelerate the healing of fractures. This study was designed to investigate the effect of once-weekly TPTD administration on vertebral stability and bony union after acute osteoporotic vertebral fracture (OVF).Overview of LiteratureOnce-weekly TPTD administration can lead to early vertebral stability and promote bony union of fractured vertebrae in patients with severe osteoporosis.MethodsForty-eight subjects with acute OVF were assigned to receive activated vitamin D3 and calcium supplementation or onceweekly subcutaneous injection of TPTD (56.5 μg) in combination with activated vitamin D3 and calcium supplementation for 12 weeks. Vertebral stability was assessed using lateral plain radiography. Vertebral height at the anterior location (VHa) and the difference in VHa {ΔVHa=VHa (supine position)−VHa (weight-bearing position)} were measured at baseline and 12 weeks after starting treatment. Bony union was defined as the absence of a vertebral cleft or abnormal motion (ΔVHa >2 mm).ResultsAlthough not significant, ΔVHa, indicating vertebral stability, tended to be lower in the TPTD group at 12 weeks (p =0.17). As for subjects with severe osteoporosis, ΔVHa at 12 weeks was significantly lower in the TPTD group than in the control group (mean ΔVHa: control group, 3.1 mm (n=15); TPTD group, 1.4 mm (n=16); p =0.02). The rate of bony union was significantly higher in the TPTD group than in the control group (control group, 40%; TPTD group, 81%; p =0.03).ConclusionsOnce-weekly TPTD administration may facilitate early bony union after acute OVF accompanied by severe osteoporosis.

Successful treatment of pathologic femoral shaft fracture associated with large arteriovenous malformations using a 3-dimensional external fixator and teriparatide: a case report

BackgroundArteriovenous malformations (AVMs) are rare congenital vascular lesions associated with early quiescence, late expansion, and, ultimately, infiltration and destruction of local soft tissue and bone. The extremities are a common location. Incidence of bony involvement by AVM has been reported as high as 31%. However, there are few reports on management of pathologic fracture associated with AVM. Teriparatide is a recombinant parathyroid hormone (PTH) analogue consisting of the 1–34 fragment of PTH. Recently, some reports have shown the ability of teriparatide to improve fracture healing. Here, we present a case of pathologic femoral shaft fracture associated with large AVMs that was treated successfully by external fixation and teriparatide.Case presentationA 68-year-old Japanese woman, previously diagnosed as having large AVMs, sustained a right femoral shaft fracture due to a fall. At the time of admission, she presented with massive swelling and venous varicosities of the right thigh. Plain radiography of the right thigh revealed femoral shaft fracture with bony erosion and calcification of soft tissue. We planned closed reduction and intramedullary nailing with a unilateral external fixator following embolization of the feeding artery. However, closed reduction using the fracture table was difficult. When we attempted open reduction, massive bleeding (1000 mL) after incision of subcutaneous tissue occurred. Finally, we carefully applied a Taylor Spatial Frame. Fracture displacement was corrected successfully and bony union was obtained with administration of teriparatide 15 months after the initial surgery. The patient is able to walk using 1 cane.ConclusionWe present the first report of pathologic fracture associated with large AVMs that achieved bony union using a 3-dimensional external fixator and teriparatide.

Safety Profiles, Pharmacokinetics, and Changes in Bone Turnover Markers After Twice‐Weekly Subcutaneous Administration of Teriparatide in Healthy Japanese Postmenopausal Women: A Single‐Blind Randomized Study

Once‐weekly injection of 56.5‐μg teriparatide formulation is a potent therapeutic agent for osteoporosis treatment. However, this treatment has an issue of difficulty in continuing the treatment by its adverse side effects including nausea, vomiting, and headaches. To reduce these adverse side effects, we conducted a randomized, single‐blind, placebo‐controlled study to examine the pharmacokinetics, changes in bone turnover markers, and safety profiles of twice‐weekly 28.2‐μg teriparatide injections. Different dosing intervals of the twice‐weekly 28.2‐μg injections were also studied. A total of 100 healthy Japanese postmenopausal women were enrolled in this multiple‐dosing study. The systemic exposure of teriparatide acetate in the twice‐weekly 28.2‐μg injection was half that of the once‐weekly 56.5‐μg injection. Changes in bone turnover markers in the twice‐weekly 28.2‐μg injection were comparable to those in the once‐weekly 56.5‐μg injection. Incidences of adverse events including nausea, vomiting, and headaches were lower in the twice‐weekly 28.2‐μg injections than those in the once‐weekly 56.5‐μg injection. Findings were similar in the twice‐weekly 28.2‐μg injections regardless of the dosing interval. Thus, the new dosing regimen using twice‐weekly 28.2‐μg injections maintained comparable efficacy to the once‐weekly 56.5‐μg injections; however, it improved the safety profile and contributed to better continuity of care with teriparatide.

Weekly Teriparatide Administration and Preoperative Anterior Slippage of the Cranial Vertebra Next to Fusion Segment < 2 mm Promote Osseous Union After Posterior Lumbar Interbody Fusion.

A multicenter case-control study. The aim of this study was to investigate the independent predictors of osseous union after posterior lumbar interbody fusion (PLIF). PLIF is usually performed to treat lumbar degenerative diseases in elderly patients. Some patients exhibit intervertebral pseudoarthrosis. We analyzed 66 elderly patients with osteoporosis who underwent PLIF from 2011 to 2014 (all women, mean age 71 years, follow-up period ≥6 months). Patients were randomly allocated to receive either treatment with weekly teriparatide, starting at 1 week postoperatively, or no teriparatide. Preoperative lumbar spine radiographs were obtained, and the amount of anterior slippage was measured. Osseous union was assessed by computed tomography at 6 months postoperatively. Thirty-three patients (50%) showed complete osseous union, while 33 did not. Teriparatide was administered in 20 (61%) patients of the union group and in 9 (27%) patients of the nonunion group (P < 0.01). The preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm was observed in 16 (49%) and 4 (12%) patients in the union and nonunion groups, respectively (P < 0.01). Multivariate regression analysis showed that teriparatide administration (odds ratio, 4.75; 95% confidence interval: 1.51-14.90; P < 0.01) and preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm (odds ratio, 5.90; 95% confidence interval: 1.53-22.70; P < 0.01) were independently associated with osseous union within 6 months after PLIF. At 6 months postoperatively, the mean femoral neck bone mineral density significantly increased by 1.1% in the union group and decreased by 1.3% in the nonunion group (P < 0.05). Weekly teriparatide administration and preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm were independent predictors of osseous union within 6 months after PLIF. Our findings suggest that biological and mechanical factors may influence the improvement of spinal fusion. 4.

Effect of daily teriparatide for delayed union of fracture neck of the femur

Background: Delayed union and nonunion of fracture neck of the femur remains a therapeutic challenge to orthopedic surgeons worldwide which is why this fracture is aptly named as unsolved fracture. Hip joint preservation surgery always remains the primary criteria in fracture neck of the femur in physiologically young patients. However, the outcome is not always satisfactory due to many factors, delayed presentation being one of them. This case series was conducted to determine and establish the role of recombinant teriparatide in fracture healing in delayed union of fracture neck of the femur. Materials and Methods: The study was done on nine cases (six males and three females) of delayed union of fracture neck of the femur with a previous history of some surgical interventions. All cases of delayed union were diagnosed by clinically and radiologically and undergone all routine blood investigations. All were administered 20 μg of teriparatide (recombinant parathormone) subcutaneous injection daily for a period of 3–5 months. Results: Eight patients who were evaluated clinically and radiologically showed satisfactory union and one case showed nonunion. One patient showed mild allergic reaction. Conclusion: This study showed that daily administration of teriparatide accelerates fracture healing in delayed union. It also enhances fracture healing throughout the period of bone remodeling phase. It also emphasizes the safety of teriparatide.

Evaluation of teriparatide effect on healing of autografted mandibular defects in rats

ObjectiveTo evaluate the effects of short-term teriparatide administration on healing of autologous bone graft in mandibular critical-size defects. Subjects and methodsA 5-mm mandibular bone defect was created and iliac bone graft was harvested in 135 rats. Rats were randomly divided into 3 groups of negative control (NC), control (C), and study (S). In groups S and C, iliac graft was placed in defect and 2 μg/kg/day teriparatide or saline, respectively, was administered for 20 days. In group NC, iliac graft was not transferred to the defect and saline was injected for 20 days. Twenty, 40, and 60 days after surgery, 15 rats in each group were euthanized and the healing process was histologically evaluated and scored using a grading system (1–6). ResultsIn group NC, defects did not heal or were predominantly filled with fibrous tissue. At day 20, bone defects in both C and S groups contained a large area of graft particles, numerous collagen fibers and some areas of new trabeculae. At the day 40, defects in group S showed a larger bone graft area, more new bone formation, smaller connective tissue area, and a higher healing score compared to group C (P < 0.05). At day 60, most of the defect in group S was filled with graft particles and mature bone while in group C, new trabecular bone formation was still underway (P < 0.05). ConclusionTeriparatide therapy improves healing of bone defects reconstructed with autograft by reducing bone graft resorption and enhancing new bone formation and maturation.

Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model

BackgroundDelay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated.MethodsFrom 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA: TP 1 μg/kg+ZA}, TP 10 μg+ZA group {T(10)+ZA: TP 10 μg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens.ResultsAbout the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups.ConclusionIt is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.

Effect of an intensive conservative therapy with daily teriparatide administration and rehabilitation for osteoporotic delayed vertebral collapse and paralysis.

Although patients with osteoporotic delayed vertebral collapse (ODVC) have frequently been treated surgically, the efficacy and limitation of conservative treatment for it have not yet been reported. The purpose of this study was to investigate the effectiveness and limitation of further intensive conservative treatment for patients with ODVC.Patients treated for ODVC from 2011 to 2014 with a follow-up period of more than 1 year were eligible. The fundamental treatment strategy consisted of surgical treatment following intensive conservative treatment with daily teriparatide and rehabilitation for 3 months. We conducted a surgical treatment for patients who could not keep standing position by themselves because of prolonged leg paralysis or intolerable back pain. We performed a logistic regression model in which surgical treatment was set as an objective variable, and other related factors including sex, age, the level of affected vertebrae, the quality of paralysis, changing rate (δ) of spinal canal encroachment, local kyphotic angle, mobility of collapsed vertebrae, EuroQol questionnaires (EQ5D), numerical rating scale (NRS), and Frankel grade as explanatory variables. We also plotted receiver operating curves (ROCs) to investigate the cutoff values of parameters at the baseline.Thirty patients (6 males and 24 females, mean age 76.7 years) were enrolled. Eventually 12 out of 30 patients avoided surgical treatment because their symptoms were improved. Logistic regression showed that δ of local kyphotic angle (odds ratio: 1.072), P = .01), mobility of collapsed vertebrae (1.063, 0.01), EQ5D (0.98, 0.04), and NRS (1.113, 0.01) were significantly correlated with the need for surgical treatments. Among the factors at baseline, only the mobility of collapsed vertebrae showed a significant value of area under a curve (AUC = 0.727, P = .008).The results that 40% of patients with ODVC did not need further surgical treatment after the intensive conservative treatment was of great significance. Patients with greater mobility of collapsed vertebrae might be treated surgically as quickly as possible.

Withdrawal of parathyroid hormone after prolonged administration leads to adipogenic differentiation of mesenchymal precursors in vivo.

Intermittent PTH-like drugs are the only approved so-called anabolic agent that increases bone mass in both mice and humans. It is well documented that PTH targets mature cells of the osteoblast lineage, with only indirect evidence of its actions on early cells of the osteoblast lineage. Using a triple transgenic mouse model that allowed labeling of very early cells of the osteoblast lineage, we traced the progeny of these into osteoblast lineage in adult mice. These early cells expressed PTH1R and multiplied when PTH (1-34) was administered daily. We also showed that the early mesenchymal cells showed accelerated differentiation into mature osteocalcin-positive osteoblasts and osteocytes. Rather surprisingly, when teriparatide administration was stopped, these early mesenchymal precursors differentiated into adipocytes. We showed that the adipogenic differentiation is accompanied by a decrease in wnt signaling in osteoblast precursors. In this review, we discuss the possible clinical relevance of this finding and the possible molecular mechanisms that contribute to this phenotype in vivo.

Enhancement of ghrelin-signaling system by Rikkunshi-To attenuates teriparatide-induced pica in rats

Teriparatide is clinically used for the treatment of osteoporosis; however, nausea is often observed in patients. Its insufficient control affects the ability to continue teriparatide therapy. Rikkunshi-To (RKT), a traditional Japanese herbal medicine, improves the gastrointestinal function via activation of the ghrelin-signaling system. We investigated the therapeutic effects of RKT on teriparatide-induced nausea in rats and the involvement of ghrelin in these effects. We previously reported that ovariectomized rats showed pica (kaolin ingestion), a behavior that can be used to assess nausea in rats, after the subcutaneous administration of teriparatide; thus, the behavior was used as an index of nausea. Ovariectomized rats were fed diets with or without RKT (1%) for 2 weeks, and then they received the subcutaneous injection of teriparatide (400 μg/kg). Teriparatide significantly increased the incidence of pica, while suppressing intestinal motility and plasma ghrelin levels in rats fed normal diets; however, rats fed diets with RKT showed improvements in all of the teriparatide-induced adverse reactions. These therapeutic effects were antagonized by a ghrelin receptor antagonist ([D-Lys3]-GHRP-6; 200 nmol/rat). These findings suggest that the enhancement of ghrelin-signaling is involved in RKT's therapeutic effect, and that RKT is a potentially useful treatment for teriparatide-induced nausea.

Humeral shaft nonunion treated with intermittent weekly administration of teriparatide (1–34 human PTH)

Humeral shaft nonunion treated with intermittent weekly administration of teriparatide (1–34 human PTH)

The role of teriparatide in tuberosity healing after reverse shoulder arthroplasty in complex proximal humeral fragility fracture.

Tuberosity healing is known to be one of the factors that increase functional outcome in Reverse Total Shoulder Arthroplasty (rTSA). In fragility fractures, tuberosity healing is difficult to be achieved. The fragment stability and bone-forming agent application become strategies to overcome this problem. The purpose of this study was to evaluate the benefit of teriparatide application to promote tuberosity union in rTSA on four-part proximal humeral fractures to achieve better functional outcome. A retrospective study of a prospectively collected shoulder arthroplasty medical record was performed. Eleven patients were included in this analysis and consisted of two groups, teriparatide and no-teriparatide groups. Patients were evaluated on the range of motions and clinical outcome using the American Shoulder Elbow Surgeon (ASES) Shoulder Score and X-ray to determine tuberosity union. The group differences were analyzed by t-test or Mann-Whitney U test with SPSS version 20.0 for Windows. The statistical analysis revealed no significant differences in mean age in both the groups. There were significant differences between teriparatide and no-teriparatide groups in external rotation (29.5° vs. 7.5°; p = 0.004), external rotation in 90° abduction (55° vs. 12.5°; p < 0.020), forward flexion (120° vs. 105°; p = 0.002) range of motions, and ASES (84.5 vs. 74.6; p = 0.019). We found clinical difference between teriparatide and no-teriparatide groups in time to achieve the initial callus (33 ± 18.3 days vs. 150 ± 42.4 days) and tuberosity consolidation (165.8 ± 70.3 days vs. 315 ± 106.1 days). Teriparatide administration supports tuberosity repair results in a high tuberosity healing rate with restoration of external rotation after rTSA in acute complex proximal humeral fractures.

Teriparatide and denosumab treatment for pregnancy and lactation-associated osteoporosis with multiple vertebral fractures: A case study

ObjectivePregnancy and lactation-associated osteoporosis (PLO) is a rare disease, which can lead to vertebral fractures in women of reproductive age. No treatment strategy for PLO has been established. Here we report a case of PLO treated with teriparatide followed by denosumab, in which remarkable improvement in bone mineral density (BMD) was achieved. Case reportA 27-year-old woman experienced severe back pain two weeks after her first delivery. PLO was diagnosed from her low BMD and multiple vertebral compression fractures. She was treated with teriparatide for 6 months, followed by denosumab. After 1 year, her BMD increase from baseline was 16.5% in L2∼4 and her pain had been relieved. ConclusionIn addition to weaning, administration of teriparatide followed by denosumab led to remarkable improvement in the patient's symptoms and BMD. Therefore, we regard this method as a promising choice for the treatment of PLO.