Improving Intraoperative Parathyroid Hormone Specimen Handling and Processing.

Surgeons request intraoperative parathyroid hormone (PTH) monitoring during parathyroidectomy procedures to confirm identification of abnormal gland tissue. Generally, a 50% decrease in the baseline PTH level indicates the abnormal tissue has been removed. A delay in collecting and processing PTH blood samples can complicate intraoperative decision making and prolong the procedure. The purpose of this quality improvement project was to develop tools to facilitate the specimen management process (eg, requesting, transporting, analyzing) for PTH blood samples and decrease the average total time required for transit and assay. We implemented a two-pronged initiative that involved improving the laboratory requisition form and creating a parathyroid tote box to contain all the needed information and supplies. The average total time for transit and assay decreased from 31.36 minutes before implementation to 22.06 minutes after implementation. Perioperative nurses expressed satisfaction with the changes and continue to use the revised process.

Bone mineral density parameters and related nutritional factors in vegans, lacto-ovo-vegetarians, and omnivores: a cross-sectional study.

Introduction: The growing prevalence of vegetarianism determines the need for comprehensive study of the impact of these diets on health and particularly on bone metabolism. We hypothesized that significant dietary differences between vegans, lacto-ovo-vegetarians, and omnivores also cause significant differences in their nutrient status, which may affect bone health. Methods: The study assessed dual-energy X-ray absorptiometry parameters in lumbar spine and femoral neck, average nutrient intake, serum nutrient concentrations, serum PTH levels, and urinary pH among 46 vegans, 38 lacto-ovo-vegetarians, and 44 omnivores. Results: There were no differences in bone mineral density (BMD) between the groups. However, the parathyroid hormone (PTH) levels were still higher in vegans compared to omnivores, despite the same prevalence of hyperparathyroidism in all groups. These findings may probably be explained by the fact that each group had its own "strengths and weaknesses." Thus, vegans and, to a lesser extent, lacto-ovo-vegetarians consumed much more potassium, magnesium, copper, manganese, and vitamins B6, B9, and C. At the same time, the diet of omnivores contained more protein and vitamins D and B12. All the subjects consumed less vitamin D than recommended. More than half of vegans and omnivores had insufficiency or even deficiency of vitamin D in the blood. Low serum concentrations of manganese with its quite adequate intake are also noteworthy: its deficiency was observed in 57% of vegans, 79% of lacto-ovo-vegetarians, and 63% of omnivores. Discussion: Currently, it is no longer possible to conclude that lacto-ovo-vegetarians have lower BMD than omnivores, as our research supported. Vegans in our study also did not demonstrate lower BMD values, only higher PTH blood concentrations, compared to omnivores, however, a large number of studies, including recent, show the opposite view. In this regard, further large-scale research is required. Vegans and lacto-ovo-vegetarians now have a variety of foods fortified with vitamins D and B12, as well as calcium. There is also a great diversity of ethically sourced dietary supplements. The found low concentrations of manganese require further investigation.

Gprc5a is a novel parathyroid hormone-inducible gene and negatively regulates osteoblast proliferation and differentiation.

Teriparatide is a peptide derived from a parathyroid hormone (PTH) and an osteoporosis therapeutic drug with potent bone formation-promoting activity. To identify novel druggable genes that act downstream of PTH signaling and are potentially involved in bone formation, we screened PTH target genes in mouse osteoblast-like MC3T3-E1 cells. Here we show that Gprc5a, encoding an orphan G protein-coupled receptor, is a novel PTH-inducible gene and negatively regulates osteoblast proliferation and differentiation. PTH treatment induced Gprc5a expression in MC3T3-E1 cells, rat osteosarcoma ROS17/2.8 cells, and mouse femurs. Induction of Gprc5a expression by PTH occurred in the absence of protein synthesis and was mediated primarily via the cAMP pathway, suggesting that Gprc5a is a direct target of PTH signaling. Interestingly, Gprc5a expression was induced additively by co-treatment with PTH and 1α, 25-dihydroxyvitamin D3 (calcitriol), or retinoic acid in MC3T3-E1 cells. Reporter analysis of a 1 kb fragment of human GPRC5A promoter revealed that the promoter fragment showed responsiveness to PTH via the cAMP response element, suggesting that GPRC5A is also a PTH-inducible gene in humans. Gprc5a knockdown promoted cell viability and proliferation, as demonstrated by MTT and BrdU assays. Gprc5a knockdown also promoted osteoblast differentiation, as indicated by gene expression analysis and mineralization assay. Mechanistic studies showed that Gprc5a interacted with BMPR1A and suppressed BMP signaling induced by BMP-2 and constitutively active BMP receptors, ALK2 (ACVR1) Q207D and ALK3 (BMPR1A) Q233D. Thus, our results suggest that Gprc5a is a novel gene induced by PTH that acts in an inhibitory manner on both cell proliferation and osteoblast differentiation and is a candidate for drug targets for osteoporosis.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12 mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0 ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0 ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

The calcium-sensing receptor has only a parathyroid hormone-dependent role in the acute response of renal phosphate transporters to phosphate intake.

The kidney controls systemic inorganic phosphate (Pi) levels by adapting reabsorption to Pi intake. Renal Pi reabsorption is mostly mediated by sodium-phosphate cotransporters NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) that are tightly controlled by various hormones including parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). PTH and FGF23 rise in response to Pi intake and decrease NaPi-IIa and NaPi-IIc brush border membrane abundance enhancing phosphaturia. Phosphaturia and transporter regulation occurs even in the absence of PTH and FGF23 signaling. The calcium-sensing receptor (CaSR) regulates PTH and FGF23 secretion, and may also directly affect renal Pi handling. Here, we combined pharmacological and genetic approaches to examine the role of the CaSR in the acute phosphaturic response to Pi loading. Animals pretreated with the calcimimetic cinacalcet were hyperphosphatemic, had blunted PTH levels upon Pi administration, a reduced Pi-induced phosphaturia, and no Pi-induced NaPi-IIa downregulation. The calcilytic NPS-2143 exaggerated the PTH response to Pi loading but did not abolish Pi-induced downregulation of NaPi-IIa. In mice with a dominant inactivating mutation in the Casr (CasrBCH002), baseline NaPi-IIa expression was higher, whereas downregulation of transporter expression was blunted in double CasrBCH002/PTH knockout (KO) transgenic animals. Thus, in response to an acute Pi load, acute modulation of the CaSR affects the endocrine and renal response, whereas chronic genetic inactivation, displays only subtle differences in the downregulation of NaPi-IIa and NaPi-IIc renal expression. We did not find evidence that the CaSR impacts on the acute renal response to oral Pi loading beyond its role in regulating PTH secretion.NEW & NOTEWORTHY Consumption of phosphate-rich diets causes an adaptive response of the body leading to the urinary excretion of phosphate. The underlying mechanisms are still poorly understood. Here, we examined the role of the calcium-sensing receptor (CaSR) that senses both calcium and phosphate. We confirmed that the receptor increases the secretion of parathyroid hormone involved in stimulating urinary phosphate excretion. However, we did not find any evidence for a role of the receptor beyond this function.

Vara Deformity and Subluxed Humeral Heads: An Unusual Sign in Pseudohypoparathyroidism.

Pseudohypoparathyroidism is a rare disorder characterized by end-organ resistance to intact parathyroid hormone (PTH) and concomitant laboratory findings of hypocalcemia and hyperphosphatemia. Radiologic evidence of the disease may manifest as a variety of bone abnormalities. This case describes an 11-year-old female with a history of repaired bilateral slipped capital femoral epiphysis who presented with a limited range of motion of the bilateral upper extremities. Laboratory findings were consistent with pseudohypoparathyroidism. Radiographs revealed subchondral resorption of bilateral clavicular heads and multiple ribs and band lucencies of proximal humeral metaphyses, along with vara deformity and inferior subluxation of the humeral heads. This presentation adds to the spectrum of potential radiographic manifestations of pseudohypoparathyroidism.

Effect of Osteoporosis Treatments on Osteoarthritis Progression in Postmenopausal Women: A Review of the Literature.

PURPOSE OF REVIEW: The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA). RECENT FINDINGS: A total of 40 relevant articles were identified. Studies were categorized into those (1) discussing estrogen and selective estrogen receptor modulators (SERMs), (2) bisphosphonates, (3) parathyroid hormone (PTH) analogs, and (4) denosumab, and (5) prior review articles. A large amount of evidence suggests that estrogen and SERMs are effective at reducing OA symptoms and disease progression. Evidence suggests that bisphosphonates, the most common medications used to treat osteoporosis, can reduce OA symptoms and disease progression. In vivo studies suggest that PTH analogs may improve the cartilage destruction associated with OA; however, few human trials have examined its use for OA. Denosumab is approved to treat osteoporosis, bone metastases, and certain types of breast cancer, but little study has been done with respect to its effect on OA. The current evidence indicates that medications used to treat osteoporosis are also effective for treating OA. Estrogen, SERMs, and bisphosphonates have the most potential as OA therapies. Less is known regarding the effectiveness of PTH analogs and denosumab in OA, and more research is needed.

Parathyroid hormone and trabectedin have differing effects on macrophages and stress fracture repair.

Stress fractures occur as a result of repeated mechanical stress on bone and are commonly found in the load-bearing lower extremities. Macrophages are key players in the immune system and play an important role in bone remodeling and fracture healing. However, the role of macrophages in stress fractures has not been adequately addressed. We hypothesize that macrophage infiltration into a stress fracture callus site promotes bone healing. To test this, a unilateral stress fracture induction model was employed in which the murine ulna of four-month-old, C57BL/6 J male mice was repeatedly loaded with a pre-determined force until the bone was displaced a distance below the threshold for complete fracture. Mice were treated daily with parathyroid hormone (PTH, 50 µg/kg/day) starting two days before injury and continued until 24 h before euthanasia either four or six days after injury, or treated with trabectedin (0.15 mg/kg) on the day of stress fracture and euthanized three or seven days after injury. These treatments were used due to their established effects on macrophages. While macrophages have been implicated in the anabolic effects of PTH, trabectedin, an FDA approved chemotherapeutic, compromises macrophage function and reduces bone mass. At three- and four-days post injury, callus macrophage numbers were analyzed histologically. There was a significant increase in macrophages with PTH treatment compared to vehicle in the callus site. By one week of healing, treatments differentially affected the bony callus as analyzed by microcomputed tomography. PTH enhanced callus bone volume. Conversely, callus bone volume was decreased with trabectedin treatment. Interestingly, concurrent treatment with PTH and trabectedin rescued the reduction observed in the callus with trabectedin treatment alone. This study reports on the key involvement of macrophages during stress fracture healing. Given these observed outcomes on macrophage physiology and bone healing, these findings may be important for patients actively receiving either of these FDA-approved therapeutics.

Real-World Experience of Using Etelcalcetide for Secondary Hyperparathyroidism in Community-Based Hemodialysis Centers in Singapore.

Introduction Chronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD). The treatment for SHPT includes synthetic vitamin D analogs, calcitriol or calcimimetics. Recently, intravenous etelcalcetide was introduced as a second-generation calcimimetic. This article provides the real-world experience of using etelcalcetide in multiethnic Asian patients receiving hemodialysis at community-based hemodialysis centers in Singapore. Methods This study was real-world evidence, generated by a retrospective clinical audit of routine clinical care of hemodialysis patients in community-based centers in Singapore who received etelcalcetide for treating SHPT. The information on the starting and maximum dose of etelcalcetide, duration of treatment on hemodialysis, parathyroid hormone (PTH) levels, dialysate calcium, concomitant medications, and reasons for discontinuation were collected from the medical records. PTH levels were collected at four-, eight-, and twelve-month intervals. Results A total of 148 patients received etelcalcetide during the study period. Ten patients died and twenty discontinued their treatment, with 118 patients remaining on treatment. Demographically, the patients included Chinese, Malay, Indians, and those belonging to other racial groups. The starting dose of etelcalcetide ranged from 2.5 mg once per week to 7.5 mg three times a week. There was a 16.8% reduction (p=<0.001) in intact-PTH after four months of therapy. Target intact-PTH level of less than 60 pmol/L, was reported as 1.4% at baseline, with 22.3% at four months (p<0.001) and 25.9% at eight months (p=0.028). Calcium and phosphate levels were also tracked as part of the safety and efficacy measures of using etelcalcetide. No symptomatic hypocalcemia was noted and phosphate levels were noted to decline significantly. Overall, the calcium-phosphate product reduced at four months (13.2%, p=<0.001) and eight months (12.7%, p<0.05). An analysis of concomitant medication usage, dialysate calcium utilized, and the side effects of etelcalcetide were also recorded. Finally, a brief descriptive analysis of the patient's subjective feedback regarding etelcalcetide was also reported, especially regarding the reduction in pill burden and overall compliance to medications. Conclusion Etelcalcetide is safe and effective for treating SHPT in multi-ethnic Asian hemodialysis patients and can be considered an alternative to oral cinacalcet. Our study showed no side effects, which was one of the key reasons for non-compliance to traditional calcimimetics. A favorable compliance profile with reduced pill burden was noted by using this intravenous calcimimetic.

Differential Effects of PTH (1-34), PTHrP (1-36), and Abaloparatide on the Murine Osteoblast Transcriptome.

Teriparatide (PTH (1-34)), PTHrP (1-36), and abaloparatide (ABL) have been used for the treatment of osteoporosis, but their efficacy long term is significantly limited. The 3 peptides exert time- and dose-dependent differential responses in osteoblasts, leading us to hypothesize they may also differentially modulate the osteoblast transcriptome. Treatment of mouse calvarial osteoblasts with 1 nM of the peptides for 4 hours results in RNA sequencing data with PTH (1-34) regulating 367 genes, including 194 unique genes; PTHrP (1-36) regulating 117 genes, including 15 unique genes; and ABL regulating 179 genes, including 20 unique genes. There were 83 genes shared among all 3 peptides. Gene ontology analyses showed similarities in Wnt signaling, cAMP-mediated signaling, ossification, but differences in morphogenesis of a branching structure in biological processes; receptor ligand activity, transcription factor activity, and cytokine receptor/binding activity in molecular functions. The peptides increased Vdr, Cited1, and Pde10a messenger RNAs (mRNAs) in a pattern similar to Rankl, that is, PTH (1-34) greater than ABL greater than PTHrP (1-36). mRNA abundance of other genes, including Wnt4, Wnt7, Wnt11, Sfrp4, Dkk1, Kcnk10, Hdac4, Epn3, Tcf7, Crem, Fzd5, Ppp2r2a, and Dvl3, showed that some genes were regulated similarly by all 3 peptides; others were not. Finally, small interfering RNA knockdowns of SIK1/2/3 and CRTC1/2/3 in PTH (1-34)-treated cells revealed that Vdr and Wnt4 genes are regulated by salt-inducible kinases (SIKs) and CREB-regulated transcriptional coactivators (CRTCs), while others are not. Although many studies have examined PTH signaling in the osteoblast/osteocyte, ours is the first to compare the global effects of these peptides on the osteoblast transcriptome or to analyze the roles of the SIKs and CRTCs.

Effects of daily versus weekly teriparatide for medication-related osteonecrosis of the jaw: A case-control study.

INTRODUCTION: Medication-related osteonecrosis of the jaw (MRONJ) is uncommon but can result in severe destruction of the jaw. This case-control study investigated the therapeutic effects of daily or weekly administration of teriparatide in the management of MRONJ using a cohort for osteonecrosis of the jaw. METHODS: Patients who were diagnosed with MRONJ and consented to teriparatide administration were assigned either to a group of daily injection or of weekly injection and completed a 4-week course of injection preoperatively and at least an 8-week course postoperatively. The control group received either the intraoperative rhBMP treatment (CG_BMP) or no additional perioperative treatment (CG_noBMP). The state of MRONJ was evaluated 2 months (T1) and 6 months (T2) postoperatively for all participants. RESULTS: Either group of daily injection (8.35 weeks ± 1.58; n = 17) or weekly injection (9.17 ± 3.79; n = 12) showed significantly faster healing than those of CG_BMP (14.40 ± 6.08; n = 25) or CG_noBMP (15.79 ± 9.79; n = 39). MRONJ was resolved completely in 24 out of 29 participants who completed the course of teriparatide injections, whereas 46.9% of CG showed delayed resolution. Multiple regression analysis indicated 7.50 times (95% CI, 1.77-31.82) more likelihood of complete resolution of MRONJ for participants with teriparatide injections. CONCLUSION: A course of daily or weekly administration of teriparatide injections may improve treatment outcomes for patients with MRONJ.

Findings of pilot study following the implementation of point of care intraoperative PTH assay using whole blood during surgery for primary hyperparathyroidism.

Objective: To report findings of pilot study using a novel point of care (POC) intraoperative parathyroid hormone (IOPTH) assay for parathyroid hormone (PTH) using whole blood during surgery for primary hyperparathyroidism (PHPT). Methods: Patients undergoing surgery for primary hyperparathyroidism from March to November 2022 where intraoperative PTH assay was performed using the NBCL CONNECT IOPTH and the laboratory PTH assay were included (group 1). The biochemistry results were reviewed to determine concordance between NBCL and lab PTH values and diagnostic test parameters of the NBCL CONNECT assay. 'In-theatre' times were then compared with a historical cohort (group 2) where the lab-based IOPTH assay alone was used. Results: Of the 141 paired samples in group I, correlation between NBCL and the lab assay was high (rho=0.82; p<0.001). PTH levels using the NBCL assay dropped satisfactorily (>50% of the basal or 0 min sample; whichever was lower - i.e. positive test) in 23 patients; giving a positive predictive value of 100%. Of the 9 patients that did not demonstrate a drop, two were true negative (negative predictive value of 22%) leading to cure after excision of another gland. Group 1 (150 mins) had a significantly shorter 'in-theatre' time compared to group 2 (167 mins) (p=0.007); despite much higher use of near infra-red autofluorescence (NIRAF) (72% vs 11.6% in group I and 2 respectively). Conclusion: The NBCL CONNECT POC IOPTH assay gives comparable results to lab based PTH assays and can be performed without need for a centrifuge or qualified technicians. Surgeons, however, need to be aware of the potential for false-negative results.

Early gene expression profiles of anabolic and catabolic molecules in murine bone after a single PTH injection.

The current study examined the gene expression profiles of anabolic and catabolic molecules after a single parathyroid hormone (PTH) injection in mice. No significant changes were observed in alkaline phosphatase area/tissue volume, tartrate-resistant acid phosphatase-positive osteoclasts, or static bone histomorphometry parameters. However, a sudden and significant decrease in Runx2 expression occurred at 1.5 h post-injection followed by immediate elevation, while sclerostin level was initially downregulated but gradually recovered. Meanwhile, Rankl expression initially increased and then returned to baseline. The prolonged elevation of anabolic molecules and transient increase in catabolic molecules may contribute to the anabolic effect of PTH treatment.

Atypical Presentation of Primary Hyperparathyroidism as Recurrent Pancreatitis: A Case Report With a Review of the Literature.

The majority of the patients with primary hyperparathyroidism (PHPT) are asymptomatic. The most common organ systems involved in PHPT are the kidneys and the skeletal system. In rare instances, acute or chronic pancreatitis may be presenting feature in PHPT patients. The association between these both diseases is still the topic of debate. Here, we put forth a case of a 52-year-old female with three episodes of pancreatitis in the last six months who was diagnosed with PHPT during the fourth episode of pancreatitis based on raised serum amylase and serum lipase levels along with ultrasonography (USG) findings of the abdomen. Pancreatitis in the absence of additional risk factors such as gallstones and alcohol abuse along with raised parathyroid hormone (PTH), hypercalcemia and osteolytic bone lesions led us towards the diagnosis of PHPT. On radio imaging such as MRI and CT scans of the neck, parathyroid adenoma was found in the posterior aspect of the right lobe of the thyroid. She was treated with parathyroidectomy. Serum calcium and PTH levels normalised postoperatively. As can be seen from our case, recurrent pancreatitis with hypercalcaemia should be evaluated for PHPT.

Using Teriparatide to Augment Healing in a Humeral Shaft Nonunion: A Case Report.

The occurrence of complications of fracture healing, such as delayed union and nonunion, is well known, but the use of pharmacotherapy for these delayed unions and nonunions has not been explored in detail. The authors describe a case of traumatic humeral shaft fracture successfully treated with once-daily administration of 20mcg of teriparatide for six months. The patient was a 22-year-old male who had been through a road traffic accident. The radiograph of the humerus shaft showed a fracture line and the displaced distal portion of the shaft of the humerus. Based on these features, the patient was diagnosed with a humeral shaft fracture. The patient underwent internal fixation with a dynamic compression plate. However, there were no signs of callus formation even after 12 weeks from the time of internal fixation. The patient was initiated with teriparatide administration and union was achieved after six months of a once-daily administration of teriparatide. Once-daily teriparatide treatment is shown to be beneficial for improving the healing of humeral shaft fractures showing delayed union.

The rationale for intermittent administration of PTH in the management of mineral and bone disorder of chronic kidney disease.

A major complication of chronic kidney disease is the derangement of mineral metabolism, leading to increased risk of fractures and cardiovascular mortality. Current therapeutic regimens are focused on reducing parathyroid hormone levels caused by secondary hyperparathyroidism, and the active vitamin D metabolite l,25(OH)2D, with limited success. It may be a more effective approach, however, if we could target the delayed response of parathyroid hormone in the early retention of phosphate following loss of renal function.We propose intermittent administration (even in stage 2 chronic kidney disease) of parathyroid hormone, known for its bone anabolic effects compared to the catabolic effects of the continuously elevated parathyroid hormone associated with the hyperparathyroid state, to mitigate the retention of phosphate. This approach may prevent the compensatory responses of the other two major calcium- and phosphate-regulating hormones (FGF-23 and l,25(OH)2D) that lead to further worsening of the derangement of mineral metabolism.In addition to its strong theoretical basis, there are data supporting the need for further research focused on the use of intermittent parathyroid hormone in the management of chronic kidney disease-mineral bone disorder.

Low-intensity pulsed ultrasound and parathyroid hormone improve muscle atrophy in estrogen deficiency mice.

Due to aging and long-term estrogen deficiency, postmenopausal women suffer muscle atrophy (MA), which is characterized by decreased muscle mass and muscle quality. Low-intensity pulsed ultrasound (LIPUS) is an acoustic wave inducing biological effects mainly by the mechanical stimulation and used as a non-invasive physical therapy for muscle repair. Parathyroid hormone (PTH) is an 84-amino-acid polypeptide, and its bioactive fragment [PTH (1-34)] has potential application in the treatment of MA. We speculate that the combination of physical therapy (i.e., the LIPUS) and regulatory hormone (i.e., the PTH) would be more effective in the treatment of MA. The objective of this study was to evaluate the individual and combined effects of LIPUS and PTH therapy on MA in estrogen deficiency mice. Seventy 8-week-old female C57BL/6J mice were used in this study and the MA model was induced by an intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD) for 20 consecutive days. The VCD-induced MA mice were randomly divided into MA, LIPUS, PTH and LIPUS + PTH (Combined) groups (n = 10/group). In the LIPUS group, the mice were treated by LIPUS in bilateral quadriceps muscles for 20 min, five times a week for 6 weeks. In the PTH group, the mice received subcutaneous injection of PTH (1-34) (80 ug/kg/d) five times a week, for 6 weeks. In the Combined group, the PTH was administrated 30 min before each LIPUS session. Hematoxylin-eosin (H&E) staining, serum biochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to evaluate the therapeutic effects of related treatments. The results showed that the MA mice had a disordered estrus cycle, significantly decreased muscle mass and myofibers cross-sectional area (CSA). After treatments, LIPUS, PTH and Combined groups had a significantly increased CSA, compared with the MA mice without treatment. In addition, Combined group had a significantly increased mRNA expression of Pax7, MyoD and MyoG, compared with LIPUS and PTH monotherapy groups. Our findings indicated that the combination of LIPUS and PTH treatment improves muscle regeneration ability, which might have potential for treating MA in postmenopausal women.

3D printed hydrogel scaffold promotes the formation of hormone-active engineered parathyroid tissue.

The parathyroid glands are localized at the back of the thyroid glands in the cervical region and are responsible for regulation of the calcium level in the blood, through specialized cells that sense Ca2+and secrete parathyroid hormone (PTH) in response to a decline in its serum level. PTH stimulates the skeleton, kidneys and intestines and controls the level of Ca2+through specialized activities. Iatrogenic removal of the parathyroid gland, as well as damage to its vascular integrity during cauterization are some of the common complications of thyroid surgery. Therefore, regeneration and/or replacement of malfunctioning parathyroid tissue is required. Tissue engineering is an emerging and promising field for patients with organ failure with recent pioneering clinical applications. The success of tissue engineering strategy depends on the use of proper cells, bioactive factors that stimulate the activities of these cells and scaffolds that are produced to recapitulate the tissue structure and support the function of the engineered tissues. 3D printing is a developing strategy for the production of these scaffolds by providing a delicate control over their structure and properties. In this study, human primary parathyroid cells were successfully isolated and their viability and ability to secrete PTH upon stimulation with different levels of Ca2+were shownin vitro. These cells were then seeded onto 3D printed alginate scaffolds and 3D bioprinted within alginate bioink, and cell viability as well as the ability to secrete PTH upon stimulation were also demonstrated. Therefore, functional hormone-active parathyroid tissue substitute was engineeredin vitrothrough 3D printed hydrogels and autologous cells.

Rare Presentation of a Common Disease: Graves' Thyrotoxicosis Presented With Non-parathyroid Hypercalcemia and Jaundice.

Graves' disease (GD) is an autoimmune thyroid disease, which is considered the most common cause of primary hyperthyroidism. GD usually manifests with symptoms such as tremors, palpitations, heat intolerance, weight loss, and specific signs on physical examination (proptosis and pretibial myxedema). However, systemic involvement is also recognized, for example, hepatic involvement in patients with GD may range from asymptomatic laboratory findings of liver function derangement (either transaminases elevations or intrahepatic cholestasis) up to hepatic failure. We describe a rare case of Graves' thyrotoxicosis presenting with severe cholestasis and non-parathyroid hormone-related hypercalcemia. An extensive evaluation for hepatobiliary causes of cholestasis, including hepatic biopsy, was entirely negative. The patient was successfully treated with methimazole with subsequent clinical and biochemical improvement.