recombinant parathyroid hormone (PTH-1-34) / Novartis, Novo Nordisk - LARVOL DELTA

Analysis of Molecular Mechanism of Erxian Decoction in Treating Osteoporosis Based on Formula Optimization Model. (PubMed, Oxid Med Cell Longev) - "Currently, OP treatments mainly include bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) antibody therapy, selective estrogen receptor modulators, teriparatide (PTH1-34), and menopausal hormone therapy...Functional pathway enrichment analysis showed that EXD exerted therapeutic effects toward OP by targeting PI3K-Akt signaling (hsa04151), calcium signaling (hsa04020), apoptosis (hsa04210), estrogen signaling (hsa04915), and osteoclast differentiation (hsa04380) via JNK, AKT, and ERK. Our method furnishes a feasible methodological strategy for formula optimization and mechanism analysis and also supplies a reference scheme for the secondary development of the TCM formula."

Journal • Orthopedics • Osteoporosis • Rheumatology

Parathyroid hormone and its related peptides in bone metabolism. (PubMed, Biochem Pharmacol) - "Although PTH(1-34), also known as teripartide, has been used clinically, it still has some disadvantages...The action mechanism of these PTH-related peptides is not exactly the same as that of PTH. Thus, the mechanisms of PTH and PTH-related peptides in bone metabolism were reviewed in this paper."

Journal • Review

PHAB: Pharmacokinetic and PHarmacodynamic Analysis and Evaluation of Teriparatide (PTH 1-34) Between Sexes (clinicaltrials.gov) - P3; N=30; Recruiting; Sponsor: University of East Anglia

New P3 trial • Musculoskeletal Diseases • Orthopedics

Antiresorptive and anabolic medications used in the perioperative period of patients with osteoporosis undergoing spine surgery: their impact on the biology of fusion and systematic review of the literature. (PubMed, Neurosurg Focus) - "Although antiosteoporosis agents are effective to varying degrees as treatments of patients with low BMD, teriparatide and bisphosphonates have been the most extensively studied with respect to spinal instrumentation. The advent of newer agents represents an area for further exploration, especially due to the current paucity of controlled investigations. It is imperative for spine surgeons to understand the mechanisms of action of these drugs and their effects on biology of fusion."

Clinical • Journal • Review • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Optimal Load for Managing Low-Risk Tibial and Metatarsal Bone Stress Injuries in Runners: The Science Behind the Clinical Reasoning. (PubMed, J Orthop Sports Phys Ther) - "Healing supplements (e.g. low-intensity pulsed ultrasound and/or recombinant parathyroid hormone therapy) may be attempted to influence tissue healing...J Orthop Sports Phys Ther, Epub 7 May 2021. doi:10.2519/jospt.2021.9982."

Clinical • Journal • Musculoskeletal Diseases • Orthopedics • Pain

Therapy with PTH 1-34 or Calcitriol and Calcium in Diverse Etiologies of Hypoparathyroidism over 27 Years at a Single Tertiary Care Center. (PubMed, Bone) - "We conclude that the effects and dose-response of PTH 1-34 treatment differ according to the etiology of hypoparathyroidism. Postsurgical hypoPT maintained mean serum calcium levels in the mid- to low-normal range while concurrently maintaining normal mean urine calcium during long-term twice-daily PTH 1-34 therapy."

Journal • Chronic Kidney Disease • Endocrine Disorders • Hypoparathyroidism • Immunology • Metabolic Disorders • Nephrology • Renal Disease

PTH1-34 promotes osteoblast formation through Beclin1-dependent autophagic activation. (PubMed, J Bone Miner Metab) - "PTH1-34 can enhance the autophagic activity of osteoblast precursors, which is involved in PTH1-34-regulated osteoblast formation. Furthermore, Beclin1, as a key autophagic regulator, plays a pivotal role in PTH1-34-regulated osteoblast precursor autophagy and osteoblastogenesis."

Journal • Osteoporosis • Rheumatology

[VIRTUAL] TransCon PTH as a Hormone Replacement Therapy for Patients with Hypoparathyroidism: 6-Month Update from the PaTH Forward Open-Label Extension (ENDO 2021) - "TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of HP...For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021."

Clinical • Endocrine Disorders • Hypoparathyroidism • Metabolic Disorders • Nephrology • Renal Disease

[VIRTUAL] Therapeutic Potentials of Dimeric Cys25 PTH(1-34) Peptide for Osteoporosis and Fracture Healing of the Bones- Buy One, Get One Free (ENDO 2021) - "For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021."

Endocrine Disorders • Hypoparathyroidism • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Renal Disease • Rheumatology

Numaswitch: an efficient high-titer expression platform to produce peptides and small proteins. (PubMed, AMB Express) - "Numaswitch was successfully employed for the production of diverse peptides and small proteins varying in length, physicochemical and functional characteristics, including Teriparatide, Linaclotide, human β-amyloid and Serum amyloid A3. Additionally, the potential of Numaswitch for a cost-efficient commercial production is demonstrated yielding > 2 g Teriparatide per liter fermentation broth in a quality meeting API standard."

Journal

Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure. (PubMed, Nefrologia) - "Hyperphosphatemia confirmed its importance in the genesis of secondary hyperparathyroidism, but also of kidney damage that was independent of PTH levels. However, inflammation, fibrosis, and cardiomyocyte growth were more closely related to PTH levels, since in the presence of similar severe hyperphosphatemia, parathyroidectomy reduced the values of inflammatory parameters, cardiac hypertrophy, and fibrosis."

Journal • Chronic Kidney Disease • Endocrine Disorders • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Secondary Hyperparathyroidism • ADAM17 • FGF23 • TNFA

Present and future scope of recombinant parathyroid hormone therapy in orthopaedics. (PubMed, J Clin Orthop Trauma) - "Teriparatide (PTH 1-34), a recombinant form of parathyroid hormone, is useful in the treatment of osteoporosis, fracture healing, non-union, stress fracture, augmentation of implant fixation with bone, and chondroprotection in osteoarthritis. The present review article will elaborate on the potential approved uses of recombinant PTH in orthopedics and its evolving role in the management of fracture osteosynthesis and other common challenging bone pathologies."

Journal • Review • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Osteoporosis • Pain • Rheumatology

Development and in vivo evaluation of intranasal formulations of parathyroid hormone (1-34). (PubMed, Drug Deliv) - "In conclusion, an effective and biosafe PTH(1-34) intranasal formulation was developed by using 10% Kolliphor HS·15 as a permeation enhancer. Intranasal formulations with higher concentrations of Kolliphor HS·15 for higher bioavailability of PTH(1-34) could be further researched."

Journal • Preclinical

An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone. (PubMed, Endocrinology) - "SPHK2 -/- and control mice were subsequently treated either with daily PTH(1-34) or vehicle for 29 days...Interestingly, suppression of Sost was blunted in the SPHK2 -/- mice when those animals were treated with an anabolic PTH regimen. We conclude that SPHK2 has an important role in mediating both normal bone remodeling and the anabolic response to PTH."

Journal • KLK2

Postsurgical hypoparathyroidism - current treatments and future prospects for parathyroid allotransplantation. (PubMed, Eur J Endocrinol) - "A prospective trial to assess the efficacy of parathyroid allotransplantation in patients with severely symptomatic protracted post-surgical hypoparathyroidism is warranted."

Journal • Review • CNS Disorders • Endocrine Disorders • Epilepsy • Hypoparathyroidism • Oncology • Osteosarcoma • Renal Disease • Sarcoma • Solid Tumor • Transplantation

Do antiosteoporotic drugs improve bone regeneration in vivo? (PubMed, Eur J Trauma Emerg Surg) - "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."

Journal • Preclinical • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

PTH(1-34) and Pelvic Fracture Healing - a Randomized Controlled Trial (clinicaltrials.gov) - P2; N=35; Active, not recruiting; Sponsor: Hospital for Special Surgery, New York; Trial primary completion date: Dec 2020 ➔ Apr 2021

Clinical • Trial primary completion date • Musculoskeletal Diseases • Orthopedics

Dynamics of Bone Cell Interactions and Differential Responses to PTH and Antibody-Based Therapies. (PubMed, Bull Math Biol) - "We also added pharmacokinetics representations of three drugs to the model, which are teriparatide (PTH(1-34)), denosumab (a RANKL antibody) and romosozumab (a sclerostin antibody), achieving excellent goodness-of-fit of human clinical data. The main attributes of each disease are qualitatively well captured by the model, for example changes in bone turnover in the disease states. We explored dosing regimens for each disease based on the combination of denosumab and romosozumab, identifying adequate ratios and doses of both drugs for subpopulations of patients in function of categories of osteoporosis and the degree of severity of the disease."

Journal • Osteoporosis • Rheumatology

PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression in MIO mice. (PubMed, Int Immunopharmacol) - "In conclusion, PTH1-34 has an obvious analgesic and anti-inflammatory effect, inhibits the matrix synthesis and alleviates the progression of osteoarthritis. In vitro, PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression via the PKA pathway and the NF-κB signaling pathways, respectively."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • MMP13 • TNFA

The receptor activator of nuclear factor κΒ ligand receptor leucine-rich repeat-containing G-protein-coupled receptor 4 contributes to parathyroid hormone-induced vascular calcification. (PubMed, Nephrol Dial Transplant) - "High PTH increases LGR4 and RANKL and decreases OPG expression in the aorta, thereby favouring VC. The hormone's direct pro-calcifying actions involve PTH1R binding and PKA activation."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease • TNFRSF11B

Simultaneous incorporation of PTH(1-34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration. (PubMed, Bioact Mater) - "Implantation of the complex hydrogel into a rat cranial defect model led to efficient bone regeneration compared to the rats treated with the hydrogel alone or with nHAP, indicating the simultaneous therapeutic effect of nHAP and PTH during the treatment process. Both the in vitro and in vivo results demonstrated that simultaneously incorporating nHAP and PTH into hydrogels shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future."

Journal • Immunology

Ligand-Dependent Effects of Methionine-8 Oxidation in Parathyroid Hormone Peptide Analogs. (PubMed, Endocrinology) - "The findings suggest that LA-PTH and PTH(1-34) engage the receptor differently in the Met8-interaction environment of the TMD bundle, and that this interaction environment can be allosterically influenced by the ECD component of the ligand-receptor complex. The findings should be useful for the future development of novel PTH-based peptide therapeutics for diseases of bone and mineral ion metabolism."

Journal • Endocrine Disorders • Hypoparathyroidism • Orthopedics • Renal Disease

Inhibition of miR-29-3p isoforms via tough decoy suppresses osteoblast function in homeostasis but promotes intermittent parathyroid hormone-induced bone anabolism. (PubMed, Bone) - "Overall, the global miR-29-3p tough decoy model represents a modest loss-of-function, which could be a relevant tool for assessing the possible impact of systemically administered miR-29-3p inhibitors. Our studies provide a potential rationale for co-administration of PTH1-34 and miR-29-3p inhibitors, to boost bone formation in severely affected osteoporosis patients, particularly in the cortical compartment."

Journal • Osteoporosis • Rheumatology • CTNNB1

Effect of duration of exposure to diets differing in dietary cation-anion difference on Ca metabolism after a parathyroid hormone challenge in dairy cows. (PubMed, J Dairy Sci) - "During PTH challenges on d 3, 8, and 13, cows received i.v. PTH 1-34 fragment at 0.05 µg/kg of body weight every 20 min for 9 h to mimic the pulsatile release of endogenous PTH...Diet-induced metabolic acidosis was observed by 24 h after dietary treatment started, resulting in increases in concentration of iCa in blood observed between 1 and 3 d. Collectively, present results indicate that tissue responsiveness to PTH and changes in blood concentrations of iCa and digestibility of Ca are elicited within 3 d of exposure to an acidogenic diet. The increased apparent digestibility of Ca compensated for the increased urinary loss of Ca resulting in similar Ca retention."

Journal • Metabolic Disorders

PTH(1‑34) activates the migration and adhesion of BMSCs through the rictor/mTORC2 pathway. (PubMed, Int J Mol Med) - "PTH(1‑34) treatment was performed with or without an mTORC1 inhibitor (20 nM rapamycin) and mTORC1/2 inhibitor (10 µM PP242)...These results indicate that PTH(1‑34) promotes BMSC migration and adhesion through rictor/mTORC2 signaling in vitro. Taken together, the results of the present study reveal an important mechanism for the therapeutic effects of PTH(1‑34) on bone‑implant osseointegration and suggest a potential treatment strategy based on the effect of PTH(1‑34) on BMSCs."

Journal • CXCR4 • FN1 • ICAM1 • PCR