Teriparatide Administration Research Articles

Teriparatide administration by the Omnipod pump: preliminary experience from two cases with refractory hypoparathyroidism.

Hypoparathyroidism (hypoPTH) in adults is mainly due to total thyroidectomy. Conventional therapies (calcium, active vitamin D) can fail to normalize calcemia, expose the patient to hypercalciuria and impact quality-of-life. Human parathormone (PTH) replacement therapy is a suitable option in these cases, although few clinical reports have been published so far. We describe two cases of patients with refractory postsurgical hypoPTH, in whom subcutaneous infusion of recombinant PTH (teriparatide) through the Omnipod® pump was initiated after failure of all other therapeutic options. Besides, we performed a review of literature of hypoPTH cases treated by continuous infusion of teriparatide. Two women aged 46 and 61 years old failed to normalize calcemia either with conventional treatments (calcium 8 g/day + calcitriol 9 mcg/day and calcium 5 g/day + calcitriol 12 mcg/day) or with thrice daily subcutaneous injections of teriparatide. As a last resort, teriparatide infusion via Omnipod® device normalized their calcemia and allowed calcium/vitamin D withdrawal, with average teriparatide dose of 23 and 32 mcg/day, respectively. The flow of teriparatide was adapted according to a protocol based on measured calcemia, under medical supervision. In the literature, 15 adult cases (13 women, mean age 44.5 ± 5.2 years old) are reported. HypoPTH was consecutive to surgery in all of them. Mean dose of teriparatide administered was 25 ± 6 mcg/day with improvement of calcemia level and quality-of-life in all patients. Continuous administration of teriparatide through Omnipod® appears as an efficient therapeutic option in refractory hypoPTH, whose administration to the patient can be assisted by medically-supervised protocol.

Effect of Weekly Teriparatide Administration Followed by Percutaneous Balloon Kyphoplasty on Post-Menopausal Osteoporotic Compression Fracture Treatment

Effect of Weekly Teriparatide Administration Followed by Percutaneous Balloon Kyphoplasty on Post-Menopausal Osteoporotic Compression Fracture Treatment

Hypoplastic femur with pathologic femoral shaft fracture associated with extensive arteriovenous malformations. A series of five cases.

Introduction:Extremities arteriovenous malformations are uncommon vascular lesions that usually go unnoticed until a fracture occurs or imaged for other medical problems. The lesion is invariably quiescent, infiltrative in nature, and leads to the destruction of soft tissue and bone. Worldwide 20-30 % incidence of arteriovenous malformations has been noted in bones. This arteriovenous malformation greatly affects bone growth as compared to the normal side and leads to pathological fracture. However, few reports on the management of such pathologic fractures associated with AVM have been published in the literature.The main problem is to decide the types of implants and whether open or closed reduction. Here, we present a case series of pathologic femoral shaft fracture associated with multiple hemangiomas in the thigh that was treated successfully by minimally invasive distal femoral locking plate fixation and teriparatide.Case Presentation:We are describing our one index case. A 39-year-old woman, otherwise healthy, sustained a fall and developed a left femoral shaft fracture. At the time of admission, she had swelling and venous varicosities and non-itchy, blanchable violet patches over the left thigh. Plain radiography of the left thigh revealed Hypoplastic femoral shaft with a markedly obliterated medullary canal with distal 1/3 rd fracture with calcification of soft tissue. We planned open reduction and distal locking femoral plating because medullary canal was very small to accommodate intramedullary nail following embolization of the feeding artery. While performing open reduction, a considerable amount of bleeding (1300 ml) after incision of subcutaneous tissue occurred. After successful fracture fixation, union was achieved with administration of teriparatide 12 months postoperatively. At present patient is able to walk using elbow support.Conclusion:We present the five cases of pathologic fracture associated with large AVMs that achieved fracture union using minimally invasive distal femoral locking plate fixation and teriparatide.

Bone microstructure changes due to once-/twice-weekly teriparatide administration: A report of five cases using high-resolution peripheral quantitative computed tomography

This study was conducted with the aim of presenting cases in which high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate changes in the bone microstructure due to once-weekly/twice-weekly administration of teriparatide (TPTD). Of osteoporosis patients who participated in a non-inferiority trial (TWICE study: once-weekly vs twice-weekly TPTD) with lumbar bone mineral density as the primary endpoint, five cases scanned by HR-pQCT before TPTD administration were analysed. Two cases were given once-weekly TPTD, three were given twice-weekly TPD, and HR-pQCT was repeated after 48 weeks. A sufficient anabolic effect of once-weekly/twice-weekly TPTD on the trabecular and cortical bone at the tibia was obtained. In addition, the average change in cortical porosity (Ct.Po) was only 0.3% in the tibia and 0.2% in the radius. These findings indicate that once-weekly and twice-weekly TPTD can be expected to improve the bone microstructure, and the increase in Ct.Po may be suppressed.

Intermittent Bi-Daily Sub-cutaneous Teriparatide Administration in Children With Hypoparathyroidism: A Single-Center Experience.

Introduction: The use of teriparatide has been reported in children with hypoparathyroidism as an investigational physiologic replacement therapy.Methods: We aimed to retrospectively report our pediatric experience of bi-daily sub-cutaneous teriparatide. Results are presented as median (25th−75th quartile). As part of the routine follow-up of these patients with hypoparathyroidism, total calcium at H0 (i.e., just before injection) and H4 (i.e., 4 h after teriparatide injection) and other biomarker parameters were regularly assessed.Results: At a median age of 10.7 (8.1–12.6) years, an estimated glomerular filtration rate (eGFR) of 110 (95–118) mL/min/1.73 m2, calcium levels of 1.87 (1.81–1.96) mmol/L and an age-standardized phosphate of 3.8 (2.5–4.9) SDS, teriparatide therapy was introduced in 10 patients at the dose of 1.1 (0.7–1.5) μg/kg/day (20 μg twice daily), with further adjustment depending on calcium levels. Six patients already displayed nephrocalcinosis. Severe side effects were reported in one child: two episodes of symptomatic hypocalcemia and one of iatrogenic hypercalcemia; one teenager displayed dysgueusia. Calcium levels at H0 did not significantly increase whilst calcium at H4 and phosphate levels significantly increased and decreased, respectively. After 12 months, eGFR, calcium and age-standardized phosphate levels were 108 (90–122) mL/min/1.73 m2, 2.36 (2.23–2.48) mmol/L, 0.5 (−0.1 to 1.5), and 68 (63–74) nmol/L, respectively, with a significant decrease in phosphate levels (p = 0.01). Urinary calcium and calcium/creatinine ratio remained stable; no nephrolithiasis was observed but two moderate nephrocalcinosis appeared.Conclusion: Intermittent teriparatide therapy significantly improves calcium and phosphate control, without increasing calciuria. It appears to be safe and well-tolerated in children.

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.

Efficacy of once-weekly teriparatide for primary prevention of glucocorticoid-induced osteoporosis: A post hoc analysis of the TOWER-GO study.

A post hoc analysis of the Teriparatide Once-Weekly Efficacy Research for Glucocorticoid-induced Osteoporosis (TOWER-GO) study was performed to examine the effect of once-weekly administration of 56.5 μg teriparatide on primary prevention of glucocorticoid-induced osteoporosis (GIOP). Of the subjects of the TOWER-GO study, 73 were included. The percentage changes from baseline in lumbar spine bone mineral density (BMD) and bone turnover markers were evaluated over 72 weeks with once-weekly teriparatide and once-weekly alendronate. The percentage change of lumbar spine BMD from baseline at 72 weeks was significantly increased in both groups. Bone formation markers were significantly increased by teriparatide administration, although they were slightly decreased by alendronate administration. Bone resorption markers were gradually decreased by teriparatide, whereas alendronate markedly decreased them within 4 weeks. No major safety concerns arose. In this primary prevention study of GIOP, comparable increases in BMD were observed between alendronate and once-weekly teriparatide. More desirable changes in bone markers were observed with teriparatide administration. These data suggest that once-weekly teriparatide is effective in primary prevention of GIOP.

Effects of the different administration frequencies of teriparatide (PTH [1-34]) on new bone formation of expanded midpalatal sutures in rats: A histomorphometric and micro-computed tomography analysis.

The aim of the study was to evaluate the effect of 4μg/kg teriparatide administered at intermittent and continuous frequencies on bone formation in the expandedmidpalatalsuture region usinghistomorphometricand micro-computed tomography (micro-Ct) analysis. Settings and sample population:In this study, 24 Sprague Dawley male rats were used. The experimental animals were divided into 3 groups as follows: Group 1: only maxillary expansion, Group 2: maxillary expansion with continuous teriparatide administration (2μg in the morning and 2μg in the evening) and Group 3: maxillaryexpansionwith intermittentteriparatide administration (daily 4μg/kg).The expansionappliance was fixed to maxillary incisors of all animals within the 5-day expansion period, followed by a 12-day retention phase. Animals were sacrificed at the end of the retention period, and specimens were evaluated by micro-Ct andhistomorphometricanalysis respectively. The results ofthe histomorphometricanalysis showed that Group 3 had the highest number of osteoblasts (1042±90.76) (P<.01). Inaddition,the results of micro-Ct analysis revealed that Group 3 had the highest bone volume/total volume (16%±0), bone mineral density (173.82±2.6mgHA/cm3 ) andleastmidpalatalsuture width (0.13±0.001mm)(P<.01). Osteoblasts number and micro-Ct analysis values of Group 2 were higher than those of Group 1 but no significant differences between them (P>.01). Intermittently administered TP (4μg/kg once a day) was seen to enhance bone formation and mineralization.In the future, it can be used in drug studies that will increase or stimulate bone formation as well as in the midpalatal suture area.

A quantitative analysis of bone lamellarity and bone collagen linearity induced by distinct dosing and frequencies of teriparatide administration in ovariectomized rats and monkeys.

The lamellar structure of bone, which endows biomechanical rigidity to support the host organism, is observed in mammals, including humans. It is therefore essential to develop a quantitative analysis to evaluate the lamellarity of bone, which would especially be useful for the pharmacological evaluation of anti-osteoporotic drugs. This study applied a current system for the semi-automatic recognition of fluorescence signals to the analysis of un-decalcified bone sections from rat and monkey specimens treated with teriparatide (TPTD). Our analyses on bone formation pattern and collagen topology indicated that TPTD augmented bone lamellarity and bone collagen linearity, which were possibly associated with the recovery of collagen cross-linking, thus endowing bone rigidity.

Effect of weekly teriparatide injections on osteoporotic fracture healing: protocol for a double-blind, randomised controlled trial

IntroductionBoth animal studies and clinical trials have shown that daily parathyroid hormone administration promotes bone fracture healing. We previously found that weekly injections of the recombinant human parathyroid hormone teriparatide...

Oral Delivery of Parathyroid Hormone Using a Triple-Padlock Nanocarrier for Osteoporosis via an Enterohepatic Circulation Pathway.

Intermittent subcutaneous (S.C.) injection of teriparatide [PTH (1-34)] is one of the effective therapies to cure osteoporosis. However, a long-term repeated administration of teriparatide by S.C. to the patients is highly challenging. Herein, a triple padlock nanocarrier prepared by a taurocholic acid-conjugated chondroitin sulfate A (TCSA) is designed to develop an oral dosage form of recombinant human teriparatide (rhPTH). Oral administration of TCSA/rhPTH to the bilateral ovariectomized (OVX) rats resulted in the recovery of the bone marrow density and healthy serum bone parameters from the severe osteoporotic conditions. Also, it enhanced new bone formation in the osteoporotic tibias. This triple padlock oral delivery platform overcame the current barriers associated with teriparatide administration and exhibited a promising therapeutic effect against osteoporosis.

Clinical Results of Vertebral Fracture Related to Diffuse Idiopathic Skeletal Hyperostosis (DISH) Which Underwent Conservative Treatment: Three Case Reports.

A vertebral fracture in a patient with diffuse idiopathic skeletal hyperostosis (DISH) is unstable due to larger moment via the long lever arm of an ankylosed spine. Therefore, surgical treatment is commonly recommended to avoid complications of nonunion and paralysis. In this report, we present 3 cases of vertebral fractures related to DISH which were primarily forced to undertake conservative treatment because of medical comorbidities and advanced age. CASE 1: A 93-year-old woman suffered from T10 vertebral fracture by a ground-level fall on her back. A trunk cast for 6 weeks was followed by brace wear for 3 months with administration of daily teriparatide. Then complete bone union was confirmed at 2 years after injury without back pain. CASE 2: An 84-year-old man suffered from T12 vertebral fracture by a fall on his back from a chair. A trunk cast for 12 weeks was followed by brace wear for 6 months with administration of daily teriparatide. Then acceptable bone union was confirmed at 1 year after the injury, and activities of daily living became independent. CASE 3: An 87-year-old woman suffered from T10 vertebral fracture due to a ground-level fall on her back when doing pruning work. Conservative treatment by trunk cast was first initiated with administration of daily teriparatide. However, delayed paralysis developed at 2 weeks after casting, so minimally invasive spinal stabilization (MISt) was performed. Bone union was obtained at 1 year after the injury without any neurological impairment. Favorable clinical courses have been obtained in 2 cases, whereas MISt was required for delayed paralysis in 1 case. Although surgical stabilization is the first-line treatment for vertebral fracture with DISH, conservative treatment can also be one of the options in cases with high operative risk due to serious medical comorbidities. However, during conservative treatment, cautious observation is necessary not to overlook the occurrence of paralysis. 4. Conservative treatment for vertebral fracture with DISH can be one of the options in cases with high operative risk due to serious medical comorbidities.

A case of a distal radial fracture with bone defects in which administration of Teriparatide (TPTD: 56.5µg/w) shortly after the operation

A case of a distal radial fracture with bone defects in which administration of Teriparatide (TPTD: 56.5µg/w) shortly after the operation

Current Concepts in the Management of Osteoporotic Vertebral Fractures: A Narrative Review.

Vertebral fractures are the most common type of osteoporotic fracture and can increase morbidity and mortality. To date, the guidelines for managing osteoporotic vertebral fractures (OVFs) are limited in quantity and quality, and there is no gold standard treatment for these fractures. Conservative treatment is considered the primary treatment option for OVFs and includes pain relief through shortterm bed rest, analgesics, antiosteoporotic drugs, exercise, and braces. Studies on vertebral augmentation (VA) including vertebroplasty and kyphoplasty have been widely reported, but there is still debate and controversy regarding the effectiveness of VA when compared with conservative treatment, and the routine use of VA for OVF is not supported by current evidence. Although most OVFs heal well, approximately 15%–35% of patients with unstable fractures, chronic intractable back pain, severely collapsed vertebra (leading to neurological deficits and kyphosis), or chronic pseudarthrosis frequently require surgery. Given that there is no single technique for optimizing surgical outcomes in OVFs, tailored surgical techniques are needed. Surgeons need to pay attention to advances in osteoporotic spinal surgery and should be open to novel thoughts and techniques. Prevention and management of osteoporosis is the key element in reducing the risk of subsequent OVFs. Bisphosphonates and teriparatide are mainstay drugs for improving fracture healing in OVF. The effects of bisphosphonates on fracture healing have not been clinically evaluated. The intermittent administration of teriparatide significantly enhanced spinal fusion and fracture healing and reduced mortality risk. Based on the current literature, there is still a lack of standard management strategies for OVF. There is a need for greater efforts through multimodal approaches including conservative treatment, surgery, osteoporosis treatment, and drugs that promote fracture healing to improve the quality of the guidelines.

Treatment strategy for atypical ulnar fracture due to severely suppressed bone turnover caused by long-term bisphosphonate therapy: a case report and literature review

BackgroundAtypical fractures may occur due to the combined effect of severely suppressed bone turnover (SSBT) caused by long-term bisphosphonate treatment and chronic repetitive bone microdamage. Atypical fracture of the ulna due to SSBT is a rare entity; there is no standardized treatment strategy for this condition. We successfully treated a patient with atypical fracture of the ulna. Herein, we present this patient, review the relevant literature, and discuss the treatment strategy.Case presentationAn 84-year-old woman presented with atypical fracture of the left ulnar shaft due to SSBT. She had a history of bisphosphonate therapy (ibandronate and alendronate) since more than 10 years; her bone turnover was severely suppressed. We performed open reduction and internal fixation (ORIF) using dual plate with some additional treatments. These included drilling and decortication, use of autogenous bone graft, low-intensity pulsed ultrasound (LIPUS) treatment, and administration of teriparatide. Finally, bone union was observed at 11 months after surgery.ConclusionsBased on the literature review and our experience with this case, ORIF alone may not be adequate to achieve bone union; drilling, decortication, and use of cancellus bone graft is important to achieve favorable outcomes. Administration of teriparatide and LIPUS may facilitate early bone union, although further studies are required to provide more definitive evidence. Furthermore, ORIF using dual plate may help avoid implant failure owing to the long time required for bone union.

Efficacy of Zoledronic Acid in Maintaining Areal and Volumetric Bone Density After Combined Denosumab and Teriparatide Administration: DATA-HD Study Extension.

Combined teriparatide and denosumab rapidly and substantially increases bone mineral density (BMD) at all anatomic sites. Discontinuation of denosumab however, results in high-turnover bone loss and increased fracture risk. The optimal way to prevent this bone loss remains undefined. This study is a preplanned extension of the DATA-HD study, where postmenopausal women with osteoporosis were randomized to receive 9 months of either 20 μg or 40 μg of teriparatide daily overlapping with denosumab (60 mg administered at months 3 and 9). At the completion of this 15-month study, women were invited to enroll in the DATA-HD Extension where they received a single dose of zoledronic acid (5 mg) 24 to 35 weeks after the last denosumab dose. Areal BMD and bone turnover markers were measured at month 27 and 42 (12 and 27 months after zoledronic acid, respectively) and spine and hip volumetric bone density by quantitative CT was measured at month 42. Fifty-three women enrolled in the DATA-HD Extension. At the femoral neck and total hip, the mean 5.6% and 5.1% gains in BMD achieved from month 0 to 15 were maintained both 12 and 27 months after zoledronic acid administration. At the spine, the mean 13.6% gain in BMD achieved from month 0 to 15 was maintained for the first 12 months but modestly decreased thereafter, resulting in a 3.0% reduction (95% CI, -4.0% to -2.0%, p < .0001) 27 months after zoledronic acid. The pattern of BMD changes between months 15 and 42 were qualitatively similar in the 20-μg and 40-μg groups. A single dose of zoledronic acid effectively maintains the large and rapid total hip and femoral neck BMD increases achieved with combination teriparatide/denosumab therapy for at least 27 months following the transition. Spine BMD was also largely, though not fully, maintained during this period. These data suggest that the DATA-HD Extension regimen may be an effective strategy in the long-term management of patients at high risk of fragility fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).

Evaluation of factors affecting the occurrence of second atypical fracture after bone union of the first atypical fracture.

Teriparatide is sometimes used in the treatment of atypical femoral fracture (AFF). Even if bone union is achieved, orthopedic physicians must consider the risk of relapse. This study aimed to investigate the factors affecting AFF recurrence, and to determine the appropriate treatment for osteoporosis after bone union. One hundred thirty-one consecutive AFFs in 113 Japanese patients were included. Eleven patients had AFF in the unaffected limb (9 patients) after the first AFF or re-fracture at the original fracture site (2 patients) after bone union of the first AFF was confirmed. We divided all patients into two groups: the second fracture group (22 AFFs in 11 patients) and non-second fracture group (109 AFFs in 102 patients). We compared clinical information between the 2 groups and investigated the factors affecting AFF recurrence using the Student t-, Welch t-, and chi-square tests. Although there was no significant difference in clinical characteristics between the 2 groups, multivariate analysis of factors associated with AFF recurrence identified short duration of treatment with teriparatide and active vitamin D3 (p=0.0408 and 0.0366, respectively) as risk factors. Even in the analysis excluding subtrochanteric AFF, short periods of teriparatide and active vitamin D3 administration were observed as risk factors (p=0.0484 and 0.0346, respectively). The administration of teriparatide for as long as possible after occurrence first AFF and the use of active vitamin D3 after completion of teriparatide therapy may be the most effective strategy to prevent the recurrence of AFF.

Effects of Combination Denosumab and High-Dose Teriparatide Administration on Bone Microarchitecture and Estimated Strength: The DATA-HD HR-pQCT Study.

In postmenopausal women at high risk of fracture, we previously reported that combined denosumab and high-dose (HD; 40 μg) teriparatide increased spine and hip bone mineral density (BMD) more than combination with standard-dose teriparatide (SD; 20 μg). To assess the effects of these combinations on bone microarchitecture and estimated bone strength, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia in these women, who were randomized to receive either teriparatide 20 μg (n = 39) or 40 μg (n = 37) during months 0 to 9 overlapped with denosumab 60 mg s.c. given at months 3 and 9, for a 15-month study duration. The 69 women who completed at least one study visit after baseline are included in this analysis. Over 15 months, increases in total BMD were higher in the HD-group than the SD-group at the distal tibia (5.3% versus 3.4%, p = 0.01) with a similar trend at the distal radius (2.6% versus 1.0%, p = 0.06). At 15 months, cortical porosity remained similar to baseline, with absolute differences of -0.1% and -0.7% at the distal tibia and -0.4% and -0.1% at the distal radius in the HD-group and SD-group, respectively; p = NS for all comparisons. Tibial cortical tissue mineral density increased similarly in both treatment groups (1.3% [p < 0.0001 versus baseline] and 1.5% [p < 0.0001 versus baseline] in the HD-group and SD-group, respectively; p = 0.75 for overall group difference). Improvements in trabecular microarchitecture at the distal tibia and estimated strength by micro-finite element analysis at both sites were numerically greater in the HD-group compared with SD-group but not significantly so. Together, these findings suggest that short-term treatment combining denosumab with either high- or standard-dose teriparatide improves HR-pQCT measures of bone density, microstructure, and estimated strength, with greater gains in total bone density observed in the HD-group, which may be of benefit in postmenopausal women with severe osteoporosis. © 2020 American Society for Bone and Mineral Research (ASBMR).

Prevention of bone loss and improvement of pain-related behavior in hind limb-unloaded mice by administration of teriparatide and bisphosphonate

Objectives There are few reports on the comparison between teriparatide (PTH) and bisphosphonate (BP) in terms of osteoporosis pain-related behavior and immunohistochemical findings. The aims of this study were to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of PTH and BP on pain and bone loss in hind limb-unloaded (HU) mice. The mechanism of osteoporotic pain in HU mice was evaluated by examining pain-related behavior and immunohistochemical findings. The effects of PTH and alendronate (ALN), a potent osteoclast inhibitor, on these parameters were also assessed. Methods Eight-week-old male ddY mice were tail-suspended for 2 weeks and assigned to four groups: hind limb-loaded (HL) mice with only tail suspension treated with vehicle; HU mice with tail suspension treated with vehicle; HU mice treated with PTH; and HU mice treated with ALN. Starting immediately after reloading, vehicle, PTH, or ALN was injected subcutaneously. After a 2-week treatment, mechanical sensitivity was examined using von Frey filaments. Bilateral hind limbs were removed for micro-computed tomography, immunohistochemical analysis, and messenger RNA (mRNA) expression analysis. Results HU mice with tail suspension developed bone loss and mechanical hyperalgesia in the hind limbs. The HU mice showed an increased osteoclasts and sclerostin-positive cells in the hind limb bone. Furthermore, PTH and ALN both prevented HU-induced bone loss and mechanical hyperalgesia in the osteoporotic animal models. Histological examination of the hind limb bone revealed that, similar to ALN, PTH inhibited the osteoclasts and sclerostin-positive cells. The mRNA levels of TNFα and IL-6 tended to decrease with ALN or PTH treatment compared with those without any treatment. Conclusions Treatment with PTH as well as BP prevented bone loss, mechanical hyperalgesia, osteoclast increase, and osteocyte increase. Similar to BP, the inhibitory effect of PTH on osteoclasts might contribute to the improvement of skeletal pain.

P0872EFFECT OF PARATHYROID HORMONE OSCILLATIONS ON BONE HEALTH: FROM OSTEO-ANABOLISM TO CATABOLISM

Abstract Background and Aims In patients with chronic kidney disease or primary hyperparathyroidism, chronically elevated parathyroid hormones (PTH) levels exert catabolic effects on the bone. In contrast, PTH oscillations (as seen in healthy subjects) or daily application of teriparatide (a form of PTH consisting of the N-terminal 34 amino acids; it is used to treat osteoporosis) promote bone formation. These differential responses have important clinical and therapeutic implications. Although the anabolic effects of PTH (and teriparatide) cycling are widely accepted, the underlying osteo-anabolic dynamics are not well understood. Method A recently developed mechanistic physiology-based model quantitating the interrelations of osteoclasts, osteoblasts and osteocytes on bone remodeling is used (Cherif et al., ΝΔΤ 2018, 33 (συππλ. 1): 165–166). The model incorporates cell-to-cell signaling pathways (i.e., RANK-RANKL-OPG), intracellular pathways, cytokines (i.e. TGFβ), PTH, sclerostin, and endocrine and paracrine feedbacks. Using the validated model, we explore the effect of altered PTH (teriparatide) administration regimen (e.g., dosing frequency and amplitude) on bone catabolism and anabolism, respectively. Results As in previous studies, the model accurately predicts differential responses of osteo-anabolic and catabolic effects of continuously and intermittently elevated PTH (teriparatide) levels, respectively. In addition, we observe that intermittent administration of PTH with a high frequency and amplitude induces bone catabolism similar to that seen in pathologies with continuously elevated PTH (i.e. primary or secondary hyperparathyroidism). We see a more than 3-fold change from baseline in osteoclastic over osteoblastic activities, resulting in a bone efflux of calcium and phosphate. Low PTH frequency with high dosing amplitude induces both osteoclastic and osteoblastic activities, but the net result is bone anabolism. Further, Fig. 1 shows a nonlinear region where high osteoblastic activities exceed osteoclastic resorption. These findings suggest the existence of optimal PTH (teriparatide) frequency-amplitude combinations that enhance anabolic gains, beyond which there can be a detrimental effect on bone. Conclusion Our results suggest that both frequency and amplitude of PTH (teriparatide) cycling affect the balance of osteo-catabolic and -anabolic effects. Understanding the underlying mechanism of differential osteo-anabolic and -catabolic responses induced by intermittent and continuous levels of PTH, respectively, may provide new therapeutic options for patients and minimize unintended consequences of intervention protocols.