PTH Group Research Articles

Daily administration of parathyroid hormone slows the progression of basic multicellular units in the cortical bone of the rabbit distal tibia.

Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis. Parathyroid hormone (PTH 1-34; Teriparatide) is an osteoanabolic treatment for osteoporosis; however, it elevates the rate of intra-cortical remodeling (activation frequency) leading, at least transiently, to increased porosity. The purpose of this study was to test the hypothesis that PTH not only increases the rate at which cortical BMUs are initiated but also increases their progression (Longitudinal Erosion Rate; LER). Two groups (n = 7 each) of six-month old female New Zealand white rabbits were both administered 30 μg/kg of PTH once daily for a period of two weeks to induce remodeling. Their distal right tibiae were then imaged in vivo by in-line phase contrast micro-CT at the Canadian Light Source synchrotron. Over the following two weeks the first group (PTH) received continued daily PTH while the second withdrawal group (PTHW) was administrated 0.9 % saline. At four weeks all animals were euthanized, their distal tibiae were imaged by conventional micro-CT ex vivo and histomorphometry was performed. Matching micro-CT datasets (in vivo and ex vivo) were co-registered in 3D and LER was measured from 612 BMUs. Counter to our hypothesis, mean LER was lower (p < 0.001) in the PTH group (30.19 ± 3.01 μm/day) versus the PTHW group (37.20 ± 2.77 μm/day). Despite the difference in LER, osteonal mineral apposition rate (On.MAR) did not differ between groups indicating the anabolic effect of PTH was sustained after withdrawal. The slowing of BMU progression by PTH warrants further investigation; slowed resorption combined with elevated bone formation rate, may play an important role in how PTH enhances coupling between resorption and formation within the BMU. Finally, the prolonged anabolic response following withdrawal may have utility in terms of optimizing clinical dosing regimens.

OR23-05 Log-term Efficacy And Safety Of Transcon PTH In Adults With Hypoparathyroidism: 52-week Results From The Open-label Extension Of The Phase 3 Pathway Trial

OR23-05 Log-term Efficacy And Safety Of Transcon PTH In Adults With Hypoparathyroidism: 52-week Results From The Open-label Extension Of The Phase 3 Pathway Trial

Hepatic artery intervention combined with immune-targeted therapy is superior to sequential therapy in BCLC-C hepatocellular carcinoma

BackgroundHepatic artery intervention combined with immunotarget therapy exerts excellent disease control and prolongs survival. However, the arrangement of hepatic artery intervention and systemic therapy confuses clinical decisions.MethodsA two-center, retrospective clinical study was approved by the Institutional Ethics Committee. From December 2018 to February 2022, patients with Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) who received targeted therapy plus PD-1 inhibitors with or without hepatic artery intervention were included. According to the treatment mode, the patients were assigned to three groups: initial hepatic artery intervention combined with immunotarget therapy, immunotarget therapy sequential hepatic artery interventional therapy, and immunotarget therapy only. The survival, response, and adverse events were compared among the three groups. Subgroup analysis and univariate and multivariate prognostic analyses were also evaluated.ResultsThe median follow-up time was 18.3 months (95% CI 16.7 to 20.0 months). A total of 163 patients with BCLC-C stage HCC were assigned to three groups: initial hepatic artery intervention plus PD-1 inhibitors plus targeted therapy (HPT, n = 66), PD-1 inhibitors plus targeted therapy followed by hepatic artery intervention (PTH, n = 56) and PD-1 inhibitors plus targeted therapy (PT, n = 41). The median progression-free survival was 8.37 months (95% CI 6.35–10.39) with HPT versus 5.3 months (95% CI 3.48–7.12) with PTH versus 6.33 months (95% CI 3.75–8.92) with PT. The progression-free survival of the HPT group was better than that of the PTH group (HR 0.66, 95% CI 0.45–0.97, p = 0.027) and PT group (HR 0.60, 95% CI 0.39–0.92, p = 0.01). The median overall survival was 14.6 months (95% CI 10.6–18.7) with HPT, 10.0 months (95% CI 8.2–11.8) with PTH and 11.3 months (95% CI 8.3–14.3) with PT. The 1-year overall survival (OS) rates in the HPT, PTH and PT groups were 50%, 33.9%, and 34.1%, respectively. Overall survival was significantly longer in the HTP group than in the PT group (HR 0.60, 95% CI 0.361–0.996, p = 0.032). Compared with the PTH group, the overall survival of the HTP group had a prolonged survival trend (HR 0.66, 95% CI 0.416–1.032, p = 0.059). All treatment modalities were deemed equally safe. Multivariate analysis suggested that the mode of treatment, albumin level, Child‒Pugh grade and hepatectomy history were independent prognostic factors for BCLC-C HCC patients.ConclusionsInitial hepatic artery intervention combined with immunotarget therapy gained survival benefits with tolerable side effects compared with immunotarget sequential hepatic artery intervention and immunotarget therapy alone. Multivariate analysis suggested that liver reserve function was closely correlated with prognosis.

Radiofrequency ablation for primary hyperparathyroidism and risk factors for postablative eucalcemic parathyroid hormone elevation

Objective To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). Methods This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. Results After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. Conclusions RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.

Parathyroid Hormone (1-34) Attenuates Cartilage Degradation and Preserves Subchondral Bone Micro-architecture in Rats with Patella Baja-Induced-Patellofemoral Joint Osteoarthritis.

Several studies have revealed that PTH1-34 may possess the potential for treating osteoarthritis (OA) and osteoporosis. However, no study has yet determined whether PTH1-34 can be used for the treatment of patella baja-induced patellofemoral joint OA (PFJOA). Thus, this study sought to assess the efficacy of PTH1-34 for the treatment of PFJOA in a rat model. Patella baja was induced in 3-month-old female Sprague-Dawley (SD) rats by patellar ligament shortening (PLS), after which the rats were randomly divided into three groups (n = 12): Sham, PLS, and PTH group (PTH + PLS, PTH1-34, 30µg/kg/d, 5days per week for 10weeks). Thereafter, radiographic imaging, macroscopic and microscopic analyses, immunohistochemistry, and microcomputed tomography (CT) analysis were performed. The appearance of PLS-induced PFJOA promoted obvious changes in the patellar position and structure in the PLS group, which were characterized by cartilage degeneration, subchondral bone microstructure deterioration, patella baja, and increasing patella length. However, these negative characteristics were markedly ameliorated by PTH1-34, which not only inhibited cartilage catabolism by decreasing MMP-13 and ADAMTS-4 but also enhanced anabolism by increasing Col-II and Aggrecan. Furthermore, the micro-CT results showed a marked improvement in subchondral bone microarchitecture. The findings presented herein demonstrated that early treatment with PTH1-34 could improve cartilage metabolism and subchondral bone health in this PFJOA model.

Parathyroid hormone enhances gap healing and osseointegration in orthopedic porous coated titanium implants: a correlative micro-computed tomographic, histomorphometric and biomechanical analysis

BackgroundParathyroid hormone, with its anabolic effect on bone formation, has shown excellent outcomes of curing postmenopausal osteoporosis as well as enhancing osseointegration around orthopaedic and stomatologic implants.The purpose of the present study is to test if low-dose intermittent PTH (1–34) treatment could achieve a satisfactory osseointegration in 2-mm peri-implant gaps, as to provide a new idea for improving the stability of such prosthesis, which will be of great clinical value.MethodsA custom-made titanium implant was implanted on the calvarium of New Zealand White rabbits. 48 male rabbits were randomly divided into control and PTH group. PTH group received subcutaneous injection of PTH (20 μg/day, 5 days/week). Animals were sacrificed at 4 and 8 weeks after surgery. Quantitative micro-computed tomography, histology and biomechanical pull-out testing were performed to evaluate the gap healing at implantation site.ResultsAnalysis of micro-computed tomography demonstrated that PTH group achieved more new bone formation in 2-mm gaps and on bone-implant interface. Quantitatively, significant differences were observed between two groups in regard to BIC and BV/TV at each time-point. Histological staining revealed that PTH group had a superiority in trabecular number, thickness, separation and better osseointegration compared to control group. As for biomechanical pull-out testing, PTH group also showed significant improvement of ultimate force than control group.ConclusionsLow-dose intermittent administration of PTH for 4 and 8 weeks enhances early osseointegration and fixation of orthopedic implants surrounded by a 2-mm gap in terms of increased bone regeneration and mechanical stability. These findings suggest PTH a potential for reducing the postoperative complications of implants by improving bone healing at peri-implant gaps.

Discontinuation of PTH therapy amplifies bone loss by increasing oxidative stress: An event ameliorated by sequential IL-17 neutralizing antibody therapy.

Osteoporosis leads to excessive bone resorption which is not accompanied by equal amount of bone formation. PTH (1-34) forms the mainstay of bone anabolic therapy. Intermittent PTH (iPTH) has the ability to reconstruct skeleton, a property not shared by other anti-resorptives. In initial phases of PTH treatment, bone formation exceeds bone resorption. However, gradually this phase is replaced by increased bone resorption. Thus, a replacement post PTH discontinuation is much needed. Studies with bisphosphonates and Denosumab post PTH withdrawal have yielded promising but variable results. Thus, there is scope for trying new combinations. Our previous studies have shown the superior skeletal effects of neutralizing IL17 antibody (NIL17) over anti-RANKL antibody. Thus, here we investigated if sequential treatment of NIL17 after PTH withdrawal (SHIFT) could serve as a promising therapeutic approach for osteoporosis treatment. Our results show that PTH withdrawal (PTH-W) led to mitigation of its anabolic effects as evidenced by reduced BMD, bone trabecular and cortical microarchitectural parameters. In the continuous PTH (PTH-C) and the Shift group, all these parameters were preserved as par with the sham group. Shift therapy also significantly increased PINP levels. Most importantly, serum CTX-I levels and osteoclast numbers, which were elevated in PTH groups were significantly suppressed in NIL17 monotherapy and shift group. Also, expression of FOXO1 and ATF-4, the main regulators of redox balance and function in osteoblasts, were found to be enhanced maximally in the sequential therapy group. Our study thus advocates use of NIL17 as a replacement therapeutic option post PTH discontinuation.

Altered static and dynamic functional network connectivity in post-traumatic headache

BackgroundPost-traumatic headache (PTH) is a very common symptom following mild traumatic brain injury (mTBI), yet much remains unknown about the underlying pathophysiological mechanisms of PTH. Neuroimaging studies suggest that aberrant functional network connectivity (FNC) may be an important factor in pain disorders. The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH.MethodsWith Institutional Review Board (IRB) approval, we prospectively recruited 50 mTBI patients with PTH, who were diagnosed with ICHD-3 beta diagnostic criteria and 39 mTBI without PTH who were well matched for age, gender and education. Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed. The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), attention network (AN), salience network (SN), visual network (VN), and cerebellum network (CN). The differences in sFNC and dFNC were determined and correlated with clinical variables using Pearson rank correlation.ResultsFor sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs. For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN. Significant reduced connectivity changes in the DMN with VN was found in State 4. Furthermore, the number of transitions (r=0.394, p=0.005) between states was positively associated with headache frequency. Additionally, dwell time (r=-0.320, p=0.025) in State 1 was negatively correlated with MoCA score.ConclusionsMTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a useful imaging biomarker for identifying and predicting mTBI with PTH.

Effect and timing of parathyroid hormone analog administration for preventing medication-related osteonecrosis of the jaws in a murine model

The aim of this study was to investigate the effect and timing of recombinant human parathyroid hormone analog (PTH) administration for preventing medication-related osteonecrosis of the jaws (MRONJ) using a murine model. After standardized MRONJ induction using zoledronic acid and dexamethasone injections, 48 female Sprague-Dawley rats were divided into four groups according to the timing of PTH administration before or after dental extraction. Rats were euthanized 3 weeks after dental extraction, followed by clinical and histologic analyses. No clinical improvements were observed in the preoperative and postoperative PTH groups, compared to controls (p = 0.638 and 0.496, respectively). However, on histological analysis, the number of empty lacunae reduced significantly, and the number of blood vessels increased in the preoperative PTH group (p = 0.004 and 0.002, respectively). The postoperative PTH group did not show significant differences for empty lacunae and blood vessels compared to controls (p = 0.075 and 0.194, respectively). The reduction in the empty lacunae and the increase in the blood vessels in the preoperative PTH group were significant compared to other groups, suggesting more viable bone tissue in this group.In perspective, preoperative PTH use may represent a better prophylactic regimen for preventing the occurrence of MRONJ after traumatic dental or surgical procedures, especially in patients with a history of long-term bisphosphonate administration or at high risk of developing MRONJ. However, the findings should be proven in further studies on other animals followed by clinical trials.

The role of deficient pain modulatory systems in the development of persistent post-traumatic headaches following mild traumatic brain injury: an exploratory longitudinal study

BackgroundPost-traumatic headache (PTH) is one of the most common and long-lasting symptoms following mild traumatic brain injury (TBI). However, the pathological mechanisms underlying the development of persistent PTH remain poorly understood. The primary purpose of this prospective pilot study was to evaluate whether early pain modulatory profiles (sensitization and endogenous pain inhibitory capacity) and psychological factors after mild TBI predict the development of persistent PTH in mild TBI patients.MethodsAdult mild TBI patients recruited from Level I Emergency Department Trauma Centers completed study sessions at 1–2 weeks, 1-month, and 4-months post mild TBI. Participants completed the following outcome measures during each session: conditioned pain modulation to measure endogenous pain inhibitory capacity, temporal summation of pain and pressure pain thresholds of the head to measure sensitization of the head, Pain Catastrophizing Scale, Center for Epidemiological Studies – Depression Scale, and a standardized headache survey. Participants were classified into persistent PTH (PPTH) and no-PPTH groups based on the 4-month data.ResultsThe results revealed that mild TBI patients developing persistent PTH exhibited significantly diminished pain inhibitory capacity, and greater depression and pain catastrophizing following injury compared to those who do not develop persistent PTH. Furthermore, logistic regression indicated that headache pain intensity at 1–2 weeks and pain inhibitory capacity on the conditioned pain modulation test at 1–2 weeks predicted persistent PTH classification at 4 months post injury.ConclusionsOverall, the results suggested that persistent PTH is characterized by dysfunctional alterations in endogenous pain modulatory function and psychological processes in the early stages following mild TBI, which likely exacerbate risk for the maintenance of PTH.

Intermittent PTH Administration Increases Bone-Specific Blood Vessels and Surrounding Stromal Cells in Murine Long Bones.

To verify whether PTH acts on bone-specific blood vessels and on cells surrounding these blood vessels, 6-week-old male mice were subjected to vehicle (control group) or hPTH [1-34] (20µg/kg/day, PTH group) injections for 2weeks. Femoral metaphyses were used for histochemical and immunohistochemical studies. In control metaphyses, endomucin-positive blood vessels were abundant, but αSMA-reactive blood vessels were scarce. In the PTH-administered mice, the lumen of endomucin-positive blood vessels was markedly enlarged. Moreover, many αSMA-positive cells were evident near the blood vessels, and seemed to derive from those vessels. These αSMA-positive cells neighboring the blood vessels showed features of mesenchymal stromal cells, such as immunopositivity for c-kit and tissue nonspecific alkaline phosphatase (TNALP). Thus, PTH administration increased the population of perivascular/stromal cellspositive forαSMA and c-kit, which were likely committed to the osteoblastic lineage. To understand the cellular events that led to increased numbers and size of bone-specific blood vessels, we performed immunohistochemical studies for PTH/PTHrP receptor and VEGF. After PTH administration, PTH/PTHrP receptor, VEGF and its receptor flk-1 were consistently identified in both osteoblasts and blood vessels (endothelial cells and surrounding perivascular cells). Our findings suggest that exogenous PTH increases the number and size of bone-specific blood vessels while fostering perivascular/stromal cellspositive forαSMA/TNALP/c-kit.

P50. Effect of systemic teriparatide (PTH1-34) versus placebo on bone mineral density (BMD) after lumbar spinal arthrodesis

BACKGROUND CONTEXT Patients undergoing decompression and non-instrumented lumbar arthrodesis may have initial bone loss after surgery, increasing their fracture risk. It is uncertain if systemic PTH has a beneficial effect on BMD after surgery. PURPOSE To determine if systemic administration of PTH will have a beneficial effect on hip and spine BMD compared to placebo in patients aged > 60 undergoing decompression and non-instrumented lumbar arthrodesis. STUDY DESIGN/SETTING Secondary analysis of data from a randomized, double-blind placebo-controlled trial of PTH vs placebo to improve fusion quality. PATIENT SAMPLE Patients enrolled in a randomized, double-blind placebo-controlled trial of PTH vs placebo to improve fusion quality. OUTCOME MEASURES Lumbar Spine and Hip BMD based on DXA scans. METHODS Patients received either 20 microgram teriparatide subcutaneously (N=44) or placebo (N=43) daily for 3 months starting day 1 after surgery. DXA scans were performed preoperatively and at 1,3,6 and 12 months post-op. ANCOVA comparing Lumbar Spine and Hip BMD in PTH vs Placebo with smoking, sex, weight, age and baseline BMD as covariates was performed. RESULTS There was a loss of Lumbar Spine BMD at 1 month postop in both groups. There was some improvement in BMD scores in the PTH group at 3 months that was not sustained at 6 and 12 months. There was a loss in Hip BMD in the placebo group at 1 and 3 months postop that was not seen in the PTH group. At 12 months postop, there was a modest decrease in BMD score for the Lumbar Spine and Hip in both groups. CONCLUSIONS Systemic PTH provides short term beneficial effect on BMD compared to placebo in patients undergoing decompression and non-instrumented lumbar arthrodesis. Some of the decline in BMD at 12 months postop is expected due to annual age-related bone loss. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Intermittent parathyroid hormone improves orthodontic retention via insulin-like growth factor-1.

This study aimed to investigate the effects of intermittent parathyroid hormone (iPTH) on the stability of orthodontic retention and to explore the possible regulatory role of insulin-like growth factor-1 (IGF-1) in this process. Forty-eight 6-week-old male Wistar rats were adopted in this study. An orthodontic relapsing model was established to investigate the effects of iPTH on orthodontic retention. In vitro, an immortalized mouse cementoblast cell line OCCM-30 was detected by flow cytometry to study the effects of iPTH on cell proliferation and apoptosis. By application of a specific IGF-1 receptor inhibitor, the role of IGF-1 was also explored. In vivo study found that daily injection of PTH significantly reduced the relapsing distance. Histological staining and ELISA assay showed faster periodontal regeneration during retention period in PTH group with increased RANKL/OPG ratio and greater amount of OCN, ALP, and IGF-1 in gingival cervical fluid (GCF). Cell experiment revealed that iPTH promoted proliferation and suppressed apoptosis of cementoblast. IGF-1 receptor inhibitor significantly restrained the anabolic effect of iPTH on OCCM-30 cells. These findings suggest that iPTH could improve the stability of tooth movement by promoting periodontal regeneration. IGF-1 is essential in mediating the anabolic effects of iPTH.

Tendon Regeneration After Partial-Thickness Peroneus Longus Tendon Harvesting: Magnetic Resonance Imaging Evaluation and In Vivo Animal Study

Background: In recent years, the use of the anterior half of the peroneus longus tendon (AHPLT) as an autograft source for ligament reconstruction has gained popularity. However, no reports are available regarding tendon regeneration after harvesting of the AHPLT. Hypothesis: When half of the tendon is preserved during tendon harvesting, the quality of the regenerated tendon is better than that of the regenerated tendon after full-thickness harvesting. Study Design: Case series; Level of evidence, 4; controlled laboratory study. Methods: A total of 21 patients who underwent AHPLT harvesting for lower extremity ligament reconstruction participated in the magnetic resonance imaging (MRI) study to evaluate tendon regeneration 1 year after the harvesting. An in vivo animal study was performed to compare the quality of the regenerated tendon after partial-thickness and full-thickness tendon harvesting. A total of 30 adult female Sprague-Dawley rats were allocated to 2 groups—15 rats underwent partial-thickness Achilles tendon harvesting (partial-thickness harvesting [PTH] group), and 15 rats underwent full-thickness Achilles tendon harvesting (full-thickness harvesting [FTH] group). The quality of the regenerated tendons was compared 180 days after tendon harvesting. Results: All 21 patients showed regeneration of the peroneus longus tendon (PLT) (homogeneously dark on both T1- and T2-weighted sequences). The cross-sectional area of the regenerated tendon divided by that of the preoperative tendon was 92.6% and 84.5% at 4 cm and 9 cm proximal to the tip of the distal fibula, respectively. In the animal study, the mean histologic score was better for the PTH group compared with the FTH group (9.17 ± 1.35 vs 14.72 ± 0.74; P < .001). The ultimate strength and the stiffness of the regenerated Achilles tendon were significantly higher for the PTH group compared with the FTH group (35.5 ± 8.3 vs 22.4 ± 8.3 N, P = .004; and 31.6 ± 7.7 vs 23.5 ± 4.8 N/mm, P = .016). Conclusion: The PLT was found to regenerate after partial-thickness harvesting on MRI. In the animal study, the quality of the regenerated tendon when half of the tendon was preserved during tendon harvesting was better than that after full-thickness tendon harvesting.

Parathyroid Hormone and Glycemic Profile in Healthy Overweight and Obese Adults

Abstract Objectives Elevated serum parathyroid hormone concentration (sPTH) is associated with higher prevalence of cardiometabolic diseases. The objective of this study was to examine the differences in cardiometabolic parameters in overweight or obese (Owt/Ob) individuals categorized into a low and high PTH group. Methods A total of 116 Owt/Ob men and women with a body mass index (BMI) between 24.7 to 43.2 kg/m2 and ages 20 to 70 years participated in this study. Blood samples were obtained for analyses of sPTH, serum 25-hydroxyvitamin D (s25OHD), serum ionized magnesium (iMg), inflammatory cytokines, insulin, fasting glucose, and triglyceride. Body composition information was measured using dual energy x-ray absorptiometry (DXA). Participants were categorized into either a Low PTH Group (sPTH &amp;lt; 55pg/mL) and High PTH Group (sPTH ≥55pg/mL). Results The mean sPTH in the Low PTH Group was 39.8pg/mL ± 10.0 (age = 33.5years ± 11.3, BMI = 28.9 kg/m2 ± 3.4), and in the High PTH Group was 79.5pg/mL ± 19.9 (age = 40.7years ± 12.5, BMI = 29.5/m2 ± 4.6). The High PTH Group had a higher fat mass % (36.7% ± 8.4, P = 0.029) and lower lean mass % (59.8% ± 7.9, P = 0.015) compared to the Low PTH Group (33.0% ± 9.7; 63.7% ± 9.1 respectively). After controlling for age, fasting blood glucose was significantly higher (P = 0.024) in the High PTH Group (97.6 mg/dL ± 3.1SEM) compared to the low PTH group (97.6 mg/dL ± 2.9SEM). There were no differences between BMI, body composition, s25OHD, iMg, inflammation cytokines, insulin, and triglyceride between PTH groups after controlling for age. Conclusions Higher sPTH was associated with a higher fasting glucose in Owt/Ob, but otherwise healthy adults. Attempts to lower sPTH in this population may delay the onset of metabolic conditions and should be explored in prospective studies. Funding Sources American Heart Association, Drexel University College of Nursing and Health Professions.

Hepatoprotective Effect of Amygdalin (Vit B17) Against Phenolphthalein Induced liver injury; involvement of Glial fibrillary acidic protein (GFAP)

BackgroundPhenolphthalein (PTH) is an odorless and colorless chemical of laxative action and multiple side effects referred mostly to the production of free . It is primarily metabolized in the liver, hence its main adverse effects occur. Amygdalin (Vit B17) have antifibrotic, antiinflammatory and antitumor activities. The histopathological and functional changes in the liver together with the postulated protective hepatoprotective effect of Amygdalin were investigated in this study. Glial fibrillary acidic protein (GFAP) was considered as a marker of liver pathological changes.Material and methods30 adult male albino rats were divided into 3 groups. Group I was the control, group II received PTH alone and group III received both PTH and Amygdalin. At day 21, the levels of serum GFAP, total protein, total bilirubin and the activities of AST and ALT and liver hydroxyproline were estimated. The liver tissue samples were examined H&amp;E, Masson’s trichrome and anti‐GFAP immunoreactive stains, and electron microscopic examination.ResultsThe liver enzymes, total bilirubin, hydroxyproline, and serum GFAP were significantly increased in group II compared with the control and in group III compared to group II. The total proteins were significantly decreased in group II in comparison to the controls and highly significantly increased in group III compared to group II. Group II showed disturbed hepatic architecture with extensive congestion, degeneration with inflammatory cell infiltration and marked collagen deposition. Group III showed preserved hepatic parenchyma and scanty inflammatory cells infiltration with decreased collagen. Group II had strong and diffuse immunoexpression and group III liver tissues were similar to the controls. The mean area percentage of GFAP immune staining showed a highly significant increased immunopositivity in group II when compared to the group I and a significant decsrease in group III compared to group II. The ultrastructure of hepatic stellate cells of group II showed dilated rough endoplasmic reticulum and loss of lipid droplets. Group III were similar to the controls.ConclusionAmygdalin treatment had a hepatoprotective effect against PTH induced liver injury and fibrosis and GFAP level could be a predictor for HSCs activation.Graphical AbstractFigure 1GFAP immune staining of the liver section of the control group (A) showing positive staining of the stellate cell and the endothelium of the sinusoids. The endothelium of the central veins is negatively stained. B: the PTH group showing strong and diffuse immunoexpression mostly perisinusoidal. C: The PTH‐Amg. group showed less marked dye expression. D: Diagram of the mean GFAP stained area percentage of the 3 animal groupsFigure 2

Effect of teriparatide on early sinus graft healing in the ovariectomized rabbit.

The purpose of this study was to determine the effect of administering intermittent parathyroid hormone 1-34 [teriparatide, (PTH)] on the maxillary sinus lift and bone grafting in osteoporotic rabbits induced by ovariectomy and glucocorticoid. Ovariectomies were performed on 20 female New Zealand white rabbits that were randomly divided into two groups: (a) the PTH group (n=10), in which 10μgkg-1 day-1 PTH was injected subcutaneously 5days a week for 5weeks (from 1week before until 4weeks after sinus surgery), and (b) the saline group (n=10), in which saline substituted PTH at the same dose, mode of administration, and duration. Bone grafting with bovine bone mineral was augmented into 13 sinuses, and bone grafts and implants were simultaneously performed in seven sinuses, in both groups. Animals were sacrificed at 4weeks after surgery. To determine whether PTH was an effective treatment for osteoporosis, we measured the bone mineral density (BMD) of the right femur using micro-computed tomography and performed radiographic and histometric analyses of the maxillary sinus surgery site. The Mann-Whitney test was used for statistical analysis. It was found that BMD increased in the femur, whereas none of the radiographic and histometric parameters differed significantly between the groups in the sinus, while there were large interindividual variations within groups. These findings suggest that intermittent PTH does not promote new bone formation in the augmented maxillary sinus of ovariectomized rabbits.

PTH1-34 improves bone healing by promoting angiogenesis and facilitating MSCs migration and differentiation in a stabilized fracture mouse model.

ObjectivePTH1-34 (parathyroid hormone 1–34) is the only clinical drug to promote osteogenesis. MSCs (mesenchymal stem cells) have multidirectional differentiation potential and are closely related to fracture healing. This study was to explore the effects of PTH1-34 on proliferation and differentiation of endothelial cells and MSCs in vitro, and on angiogenesis, and MSCs migration during fracture healing in vivo.MethodsMice with stabilized fracture were assigned to 4 groups: CON, PTH (PTH1-34 40 μg/kg/day), MSC (transplanted with 105 MSCs), PTH+MSCs. Mice were sacrificed 14 days after fracture, and callus tissues were harvested for microCT scan and immunohistochemistry analysis. The effects of PTH1-34 on angiogenesis, and MSCs differentiation and migration were assessed by wound healing, tube formation and immunofluorescence staining.ResultsTreatment with either PTH1-34, or MSCs promoted bone healing and vascular formation in fracture callus. The callus bone mass, bone volume, and bone mineral density were all greater in PTH and/or MSC groups than they were in CON (p<0.05). PTH1-34 increased small vessels formation (diameter ≤50μm), whereas MSCs increased the large ones (diameter >50μm). Expression of CD31 within calluses and trabecular bones were significantly higher in PTH1-34 treated group than that of not (p<0.05). Expression of CD31, VEGFR, VEGFR2, and vWF was upregulated, and wound healing and tube formation were increased in MSCs treated with PTH1-34 compared to that of control.ConclusionsPTH1-34 improved the proliferation and differentiation of endothelial cells and MSCs, enhancing migration of MSCs to bone callus to promote angiogenesis and osteogenesis, and facilitating fracture healing.

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.

Do antiosteoporotic drugs improve bone regeneration in vivo?

Treatment of complex fractures in the elderly is a challenge for operative reconstruction due to degraded bone structure. Early peri-operative bone anabolic treatment could improve new bone formation, avoid implant loosening and accelerate fracture healing. To compare the osteoanabolic potential of different drugs after distraction osteogenesis, 168 female Sprague-Dawley rats underwent lengthening of the right femur using a monolateral external fixator. Animals were randomly divided into six groups: vehicle-injected group, PTH(1-34), raloxifen, strontium ranelate, alendronate and simvastatin. Histomorphometry, CT-scanning, DEXA- and biomechanical analysis were performed to evaluate new bone formation, callus volume, mineralisation and biomechanical strength. Expression of bone metabolic mediators and differentiation indicators of distracted and intact bone were examined by RT-PCR and western blot. Histological analysis showed significant increase of the bone mass after treatment with PTH(1-34), raloxifen and strontium ranelate (p = 0.02). Raloxifen increased bone mineral content (BMC) of the whole distracted femur significantly (p = 0.007). Callus volume was significantly larger in the PTH(1-34), raloxifen and simvastatin groups (p = 0.001) compared to control. Ultimate load of distracted new formed bone was increased in PTH(1-34) and raloxifen groups. It seems that PTH(1-34) and raloxifen have a stronger effect on bone where a repair response is activated. Strontium ranelate demonstrates similar effects to PTH regarding new bone formation but shows low values for mineralisation and biomechanical strength. This study suggests that peri-operative treatment of complex and/or osteoporotic fractures with PTH(1-34) and raloxifen might be useful as a stimulator of bone formation and mineralisation to shorten the consolidation time in humans.