Central giant cell granuloma of the jaws-long-term clinical and radiological outcomes of surgical and pharmacological management.

OBJECTIVES: To compare long-term results of different treatment modalities in central giant cell granuloma of the maxillofacial-skeleton. Primary resection may result in major defects. Alternative treatments include pharmacological agents. As yet there has been no consensus on the use of the variety of treatment options, and few studies have reported clarifying long-term results. MATERIALS AND METHODS: This retrospective study on 22 patients with 25 lesions evaluated clinical, radiological and histological features, treatment preformed and lesion recurrence. Success was defined as regression/calcification and failure as recurrence, progression or un-responsiveness. RESULTS: Of the presenting patients, 77% were under age 40. Lesion prevalence was higher in the anterior mandible and left posterior maxilla. Most cases exhibited pain, tooth-mobility or mucosal-expansion. The appearance was predominantly unilocular in the maxilla and multilocular in the mandible, which also exhibited higher prevalence of cortical perforation. Up to 80% of lesions were classified as aggressive. Intralesional steroids/calcitonin were used in 7 cases. Mean follow-up was 39.8 months. Two cases showed recurrence. In 71% of the cases treated pharmacologically, calcification/regression were observed. CONCLUSIONS: Our analysis indicates better outcomes using a combined approach, including both pharmacological and surgical treatments in large aggressive lesions. Pharmacological treatment resulted in decreased size or well-defined lesions, thus reducing the need for extensive bone resection. Dual treatment with corticosteroids and calcitonin showed no superior outcomes, but a larger cohort should be assessed. CLINICAL RELEVANCE: There are several protocols for treatment of central-giant-cell-granuloma lesions, but most are not fully established. It is important to report results that contribute to the establishment of proven protocols. This report attempts to establish the relevance of the combined approach: pharmacological treatment followed by surgical resection.

Calcitonin in the Treatment of Phantom Limb Pain: A Systematic Review.

INTRODUCTION: Phantom limb pain (PLP) refers to pain perceived in a part of the body removed by amputation or trauma. Despite the high prevalence of PLP following amputation and the significant morbidity associated with it, robust therapeutic approaches are currently lacking. Calcitonin, a polypeptide hormone, has recently emerged as a novel analgesic with documented benefits in the treatment of several pain-related conditions. METHODS: We present a systematic review that comprehensively evaluates the analgesic effects of calcitonin for patients with PLP. We searched MEDLINE, OLDMEDLINE, and PubMed Central databases with the key words "calcitonin" "phantom limb pain" and "phantom pain" to identify clinical studies evaluating the efficacy or effectiveness of calcitonin administration, in any form and dose, for the treatment of PLP. Additionally, Google Scholar was searched manually with the search term "calcitonin phantom limb pain". All four databases were searched from inception until 1 December 2022. The methodological quality of each included study was assessed using the Downs and Black checklist and the GRADE criteria were used to assess effect certainty and risk of bias. RESULTS: Our search identified 4108 citations, of which six ultimately met the criteria for inclusion in the synthesis. The included articles described a mix of open-label (n = 2), prospective observational cohort (n = 1), and randomized clinical trials (n = 3). The most common treatment regimen in the current literature is a single intravenous infusion of 200 IU salmon-derived calcitonin. CONCLUSION: The available evidence supported the use of calcitonin as either monotherapy or adjuvant therapy in the treatment of PLP during the acute phase, while the evidence surrounding calcitonin treatment in chronic PLP is heterogeneous. Given the limited treatment options for the management of PLP and calcitonin's relatively wide therapeutic index, further research is warranted to determine the role that calcitonin may play in the treatment of PLP and other pain disorders.

An observational study on monoclonal antibodies against calcitonin-gene-related peptide and its receptor.

BACKGROUND AND PURPOSE: Based on their pharmacological target, two classes of calcitonin-gene-related peptide (CGRP) monoclonal antibodies (mAbs) have been identified: antibodies against the CGRP ligand-galcanezumab, fremanezumab, eptinezumab-and antibodies against the CGRP receptor (CGRP-R), erenumab. The aim of the present study was to compare anti-CGRP versus anti-CGRP-R mAbs in patients with high frequency episodic and chronic migraine. METHODS: All patients on monthly treatment with anti-CGRP mAbs with an available 6 months' follow-up at January 2022 were included. Data on efficacy outcome were collected following one (T1), three (T3) and six (T6) months of treatment, and included monthly headache/migraine days, the Migraine Disability Assessment Scale (MIDAS) and Headache Impact Test 6 (HIT-6) scores, pain intensity, analgesics consumption and response rates (>50% headache days reduction compared to baseline). RESULTS: In all, 152 patients were enrolled, of whom 68 were in treatment with anti-CGRP mAbs (49 galcanezumab, 19 fremanezumab) and 84 with the anti-CGRP-R (erenumab). MIDAS scores were significantly lower in the anti-CGRP group at T1 and T3 (respectively p < 0.02 and p < 0.03) as well as the number of mean migraine days at T3 (p < 0.01). At T3 and T6 outcome measures were comparable, although a significantly higher percentage of super-responders was found in the anti-CGRP group (respectively p < 0.04 and p < 0.05), with a similar overall percentage of responders. CONCLUSIONS: The present study on a real-world sample confirms the beneficial effect of both anti-CGRP and anti-CGRP-R mAbs, with a more favorable outcome for anti-CGRP antibodies.

Consider this tool to reduce antibiotic-associated adverse events in patients with sepsis.

Predictive biomarker procalcitonin can aid clinical decision-making on continued antibiotic treatment in this patient population.

How to best use procalcitonin to diagnose infections and manage antibiotic treatment.

OBJECTIVES: Procalcitonin (PCT) is a host-response biomarker that has shown clinical value for assessing the likelihood of bacterial infections and guiding antibiotic treatment. Identifying situations where PCT can improve clinical care is therefore highly important. METHODS: The aim of this narrative review is to discuss strategies for the usage and integration of PCT into clinical routine, based on the most recent clinical evidence. RESULTS: Although PCT should not be viewed as a traditional diagnostic marker, it can help differentiate bacterial from non-bacterial infections and inflammation states - particularly in respiratory illness. Several trials have found that PCT-guided antibiotic stewardship reduces antibiotic exposure and associated side-effects among patients with respiratory infection and sepsis. Studies have demonstrated that patient-specific decisions regarding antibiotic usage is highly complex. Factors to consider include: the clinical situation (with a focus on the pretest probability for bacterial infection), the acuity and severity of presentation, as well as PCT test results. Low PCT levels help rule out bacterial infection in patients with both low pretest probability for bacterial infection and low-risk general condition. In high-risk individuals and/or high pretest probability for infection, empiric antibiotic treatment is mandatory. Subsequent monitoring of PCT helps track the resolution of infection and guide decisions regarding early termination of antibiotic treatment. CONCLUSIONS: PCT possesses high potential to improve decision-making regarding antibiotic treatment - when combined with careful patient assessment, evidence-based clinical algorithms, and continuous notification and regular feedback from all antibiotic stewardship stakeholders. Medical Journals such as Clinical Chemistry and Laboratory Medicine (CCLM) have played a critical role in reviewing and dissemination the high-quality evidence about assays for PCT measurement, observational research regarding association with outcomes among different populations, and interventional research proofing its effectiveness for patient care.

[Novel Migraine Treatment: From Bench to Bedside].

Discovering that calcitonin-related peptide (CGRP) plays a key role in migraine pathophysiology has allowed us to develop new approaches for acute and preventive treatment. Monoclonal antibodies against CGRP and its receptor offer considerable improvements over existing drugs for migraine prevention. The serotonin 1F (5-HT 1F) receptor agonist lasmiditan can across the blood-brain barrier and act on peripheral and central nervous system sites without vasoconstriction by activating 5-HT1B. Migraine treatment has reached a new era with the development of drugs by translating basic research findings from the bench to the bedside.

A narrative review of the calcitonin peptide family and associated receptors as migraine targets: Calcitonin gene-related peptide and beyond.

OBJECTIVE: To summarize the pharmacology of the calcitonin peptide family of receptors and explore their relationship to migraine and current migraine therapies. BACKGROUND: Therapeutics that dampen calcitonin gene-related peptide (CGRP) signaling are now in clinical use to prevent or treat migraine. However, CGRP belongs to a broader peptide family, including the peptides amylin and adrenomedullin. Receptors for this family are complex, displaying overlapping pharmacologic profiles. Despite the focus on CGRP and the CGRP receptor in migraine research, recent evidence implicates related peptides and receptors in migraine. METHODS: This narrative review summarizes literature encompassing the current pharmacologic understanding of the calcitonin peptide family, and the evidence that links specific members of this family to migraine and migraine-like behaviors. RESULTS: Recent work links amylin and adrenomedullin to migraine-like behavior in rodent models and migraine-like attacks in individuals with migraine. We collate novel information that suggests females may be more sensitive to amylin and CGRP in the context of migraine-like behaviors. We report that drugs designed to antagonize the canonical CGRP receptor also antagonize a second CGRP-responsive receptor and speculate as to whether this influences therapeutic efficacy. We also discuss the specificity of current drugs with regards to CGRP isoforms and how this may influence therapeutic profiles. Lastly, we emphasize that receptors related to, but distinct from, the canonical CGRP receptor may represent underappreciated and novel drug targets. CONCLUSION: Multiple peptides within the calcitonin family have been linked to migraine. The current focus on CGRP and its canonical receptor may be obscuring pathways to further therapeutics. Drug discovery schemes that take a wider view of the receptor family may lead to the development of new anti-migraine drugs with favorable clinical profiles. We also propose that understanding these related peptides and receptors may improve our interpretation regarding the mechanism of action of current drugs.

RREB1 promotes the development of parafollicular carcinogenesis through the Ras-Raf-1-ELK3 signaling pathway.

Thyroid cancer (TC) is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC) is derived from parathyroid follicle cells (C cells) secrete calcitonin, accounting for approximately 5-10% of all thyroid cancers. The malignancy is between differentiated and undifferentiated thyroid cancer and undifferentiated thyroid cancer and has a relatively poor prognosis. In MTC tumor cells, RREB1 regulates the differentiation of parathyroid cells via RAS-Raf-1-ELK3 signaling and induce calcitonin secretion. Therefore, it is easy to induce parathyroid parafollicular cells canceration and medullary thyroid carcinoma. Here, we investigated the correlation between RREB1, RAS-Raf-1-ELK3 signaling pathway and medullary thyroid carcinoma with various phases. Our results suggest that RREB1 promotes parafollicular carcinoma through the Ras-Raf1-elk3 signaling pathway, providing a rationale to further investigate the role of RREB1 in parafollicular carcinoma. It provides theoretical guidance for the clinical treatment of medullary thyroid cancer.

Safety evaluation of oral calcitonin-gene-related peptide receptor antagonists in patients with acute migraine: a systematic review and meta-analysis.

OBJECTIVE: Calcitonin gene-related peptide (CGRP) receptor antagonists have been suggested as novel treatments for acute migraine. This study aimed to use meta-analysis to compare the safety and tolerability of five existing oral CGRP receptor antagonists (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant) with that of a placebo or triptans against acute migraine. METHODS: Five prominent databases were searched to identify randomized controlled trials on this topic. The primary safety outcomes of interest were any adverse events (AEs) and treatment-related adverse events (TRAEs), and secondary outcomes were individual events, namely diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting. RESULTS: Fifteen studies met the eligibility criteria and were examined in detail. Although, compared to placebo, oral CGRP receptor antagonists significantly increased the incidence of any AEs (risk ratio [RR] = 1.15; 95% confidence interval [CI] = 1.07-1.23), there was no difference in the incidence of TRAEs (RR = 1.18; 95% CI = 1.00-1.38). Moreover, CGRP receptor antagonists were safer than triptans with respect to primary safety outcomes, such as any AEs (RR = 0.78; 95% CI = 0.63-0.98) and TRAEs (RR = 0.68; 95% CI = 0.58-0.79). CONCLUSION: Despite oral CGRP receptor antagonists posing a significantly higher risk of AEs when compared to placebo, CGRP receptor antagonists have a favorable safety profile compared to triptans. Our findings inform strategies to enhance safety and tolerability in the treatment of acute migraine.

Successful Treatment with Selpercatinib for Ectopic Cushing's Syndrome Due to Medullary Thyroid Cancer.

Selpercatinib, a RET kinase inhibitor, is an effective treatment for patients with medullary thyroid cancer with RET mutations. In this paper, we present the case of a 62-year-old man with ectopic Cushing's syndrome due to medullary thyroid cancer who received treatment with selpercatinib. Six months later, all the cushingoid features had resolved, and s-calcitonin had decreased from 580 pmol/L to 3.5 pmol/L (normal < 3). After further 6 months, s-calcitonin had normalized (1.5 pmol/L), and radiological evaluation showed a profound tumour volume reduction. We are aware of two other cases where treatment with selpercatinib has also been successful. Thus, selpercatinib may be a promising treatment alternative in patients with ectopic Cushing's syndrome due to medullary thyroid cancer, especially when other treatment options are ineffective or not tolerated.

Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target - an fMRI study.

Background: Monoclonal antibodies (mAbs) against calcitonin gene-related peptides (CGRP) are novel treatments for migraine prevention. Based on a previous functional imaging study which investigated the CGRP receptor mAb (erenumab), we hypothesized that (i) the CGRP ligand mAb galcanezumab would alter central trigeminal pain processing; (ii) responders to galcanezumab treatment would show specific hypothalamic modulation in contrast to non-responders; and (iii) the ligand and the receptor antibody differ in brain responses. Methods: Using an established trigeminal nociceptive functional magnetic imaging paradigm, 26 migraine patients were subsequently scanned twice: before and 2-3 weeks after administration of galcanezumab. Results: We found that galcanezumab decreases hypothalamic activation in all patients and that the reduction was stronger in responders than in non-responders. Contrasting erenumab and galcanezumab showed that both antibodies activate a distinct network. We also found that pre-treatment activity of the spinal trigeminal nucleus (STN) and coupling between the STN and the hypothalamus covariates with the response to galcanezumab. Conclusions: These data suggest that despite relative impermeability of the blood-brain barrier for CGRP mAb, mAb treatment induces certain and highly specific brain effects which may be part of the mechanism of their efficacy in migraine treatment. Funding: This work was supported by the German Ministry of Education and Research (BMBF) of ERA-Net Neuron under the project code BIOMIGA (01EW2002 to AM) and by the German Research Foundation (SFB936-178316478-A5 to AM). The funding sources did not influence study conduction in any way. Clinical trial number: The basic science study was preregistered in the Open Science Framework (https://osf.io/m2rc6).

THERAPY OF ENDOCRINE DISEASE: Amylin and calcitonin - physiology and pharmacology.

Type 2 diabetes is a common manifestation of metabolic dysfunction due to obesity and constitutes a major burden for modern health care systems, in concert with the alarming rise in obesity worldwide. In recent years, several successful pharmacotherapies improving glucose metabolism have emerged and some of these also promote weight loss, thus, ameliorating insulin resistance. However, the progressive nature of type 2 diabetes is not halted by these new anti-diabetic pharmacotherapies. Therefore, novel therapies promoting weight loss further and delaying diabetes progression are needed. Amylin, a beta cell hormone, has satiating properties and also delays gastric emptying and inhibits postprandial glucagon secretion with the net result of reducing postprandial glucose excursions. Amylin acts through the six amylin receptors, which share the core component with the calcitonin receptor. Calcitonin, derived from thyroid C cells, is best known for its role in humane calcium metabolism, where it inhibits osteoclasts and reduces circulating calcium. However, calcitonin, particularly of salmon origin, has also been shown to affect insulin sensitivity, reduce the gastric emptying rate and promote satiation. Preclinical trials with agents targeting the calcitonin receptor and the amylin receptors, show improvements in several parameters of glucose metabolism including insulin sensitivity and some of these agents are currently undergoing clinical trials. Here, we review the physiological and pharmacological effects of amylin and calcitonin and discuss the future potential of amylin and calcitonin-based treatments for patients with type 2 diabetes and obesity.

Evaluation of a Pharmacy-Driven Calcitonin Protocol for Treating Hypercalcemia in Hospitalized Patients: A Multisite Study.

BACKGROUND: The dramatic increase in the acquisition cost of injectable calcitonin led to creating a pharmacy-driven calcitonin protocol to improve the appropriate use of calcitonin and other treatment modalities for hypercalcemia. OBJECTIVE: This study aimed to characterize the use of calcitonin before and after implementation of a pharmacy-driven calcitonin protocol. METHODS: This was a multi-center, retrospective study of the use of injectable calcitonin in adult hospitalized patients with hypercalcemia. The study included patients treated with calcitonin from October 2014 to September 2016 and from October 2017 to September 2019. The primary outcomes were percentage of patients with a complete response, partial response, and non-responders. The secondary outcomes were time to relapse, duration of partial response, number of doses, and associated costs of calcitonin. RESULTS: Of the 131 patients included in this study, 93 were included in a pre-protocol group and 38 were included in a post-protocol group. The primary outcome of complete response by 3 days was met in 28% of patients in the pre-protocol group and 53% of patients in the post-protocol group (P = 0.007). Calcitonin spending in dollars in the pre-protocol group was $818,956 compared to $224,320 in the post-protocol group; a difference of $594,636. CONCLUSION: Implementation of a pharmacy-driven calcitonin protocol effectively improved calcium levels, reduced inappropriate calcitonin use, and reduced calcitonin spending during a period of 2 fiscal years.

A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation. MATERIALS AND METHODS: The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width. RESULTS: In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4-8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011). CONCLUSION: Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug. LEVEL OF EVIDENCE: Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.

Hypercalcemia of Malignancy and Acute Pancreatitis.

OBJECTIVES: Hypercalcemia of malignancy confers a poor prognosis. This systematic review evaluated published cases of hypercalcemia of malignancy presenting with acute pancreatitis (AP), in terms of clinical presentation and outcomes. METHODS: A comprehensive review of PubMed and Embase until March 18, 2020, was conducted. Studies were included if they reported on patients with hypercalcemia of malignancy and AP with attempts to exclude other etiologies of hypercalcemia and AP. Two independent reviewers selected and appraised studies using the Murad tool. RESULTS: Thirty-seven cases were identified. Mean (standard deviation) age was 44.8 (2.46) years. Mean (standard deviation) presenting corrected calcium was 14.5 (0.46) mg/dL. Parathyroid carcinoma (21.6%) and multiple myeloma (21.6%) were the most common malignancies. Cases were classified as severe (37.8%), mild (21.6%), and moderately severe (18.9%), whereas 21.6% did not report severity. Necrotizing pancreatitis developed in 21.6% of cases. Most cases were treated with intravenous hydration and bisphosphonates or calcitonin/calcitonin analogues. Mortality was 32.4% during the same presentation of AP. Among mortality cases, 10 of 12 had severe AP, and 5 of 12 had necrotizing pancreatitis. Degree of hypercalcemia did not influence mortality. CONCLUSION: Acute pancreatitis associated with hypercalcemia of malignancy is rare. One in 3 patients with this presentation may not survive AP.

Effects of Teriparatide versus Salmon Calcitonin Therapy for the Treatment of Osteoporosis in Asia: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The objective of this meta-analysis was to compare the efficacy and safety of teriparatide versus salmon calcitonin for the treatment of osteoporosis in Asian patients and to investigate whether the results of global studies could be applicable to Asian patients. METHODS: PubMed, OVID, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE up to December 2018 were searched. Eligible randomized controlled trials (RCTs) that compared teriparatide versus salmon calcitonin in Asian osteoporosis population were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data synthesis, and Cochrane Collaboration software Review Manager 5.3 was used to analyze the pooled data. RESULTS: Three RCTs involving 529 patients were included (mean age 68.7 yr; 93.4% females; mean follow-up 6 months); outcome measures included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine; bone markers and adverse events. We found that the period of 6-months of teriparatide treatment was helpful for the improvement of the BMD of lumbar vertebra, however, the improvement of BMD was not significant in the femoral neck and total hip joint. There was a positive correlation between bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCN) and the response of Asian patients to subcutaneous injection of 20 micrograms per day of teriparatide. The proportion of the occurrence of adverse effects was more obvious in the teriparatide group compared with salmon calcitonin, but there was no significant difference. CONCLUSION: Results suggested that the use of teriparatide could improve the lumbar BMD by shortterm (six months) application in Asian osteoporosis patients, which is beneficial to the patients who cannot tolerate adverse events of long-term treatment. The BSAP and OCN bone markers could be useful to monitor the responses of Asian osteoporosis patients to teriparatide treatment. Finally, both of teriparatide and salmon calcitonin were well tolerated by Asian patients.

A Rare Case of Nontraumatic Thoracic Compression Fracture in a 28-Year-Old Man.

ABSTRACT: A 28-yr-old African American man with a history of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome, tobacco use, and sickle cell trait was referred to a physiatrist at a multidisciplinary spine center with a 1-yr history of nontraumatic thoracic back pain that had significantly worsened over the previous 4 wks. In the context of recurrent infections requiring hospital admissions and the patient's immunosuppressed status, magnetic resonance imaging of his thoracic spine was obtained, showing an acute or subacute anterior compression deformity of the T7 vertebral body. He was subsequently provided with a hyperextension brace, physical therapy referral, and a trial of intranasal calcitonin. The patient reported significant improvement in pain at his 3-mo follow-up appointment and continued to show pain and functional improvement in physical therapy sessions up to 6 mos later.

Bisphosphonate Versus Bisphosphonate and Calcitonin for the Treatment of Moderate to Severe Hypercalcemia of Malignancy.

BACKGROUND: Historically, intravenous (IV) bisphosphonates with calcitonin are the treatment of choice for hypercalcemia of malignancy. However, evidence is lacking. OBJECTIVE: The objective of this study was to compare the use of bisphosphonate versus bisphosphonate with calcitonin for moderate to severe hypercalcemia of malignancy. METHODS: This was a retrospective study evaluating patients who received bisphosphonate and/or calcitonin for treatment of moderate to severe hypercalcemia of malignancy. Patients received usual care plus either (1) bisphosphonate or (2) bisphosphonate with calcitonin. The primary outcome was change in corrected serum calcium concentrations 48 hours after treatment. Secondary outcomes included corrected calcium levels, incidence of normocalcemia and hypocalcemia, time to normocalcemia, hospital length of stay, and cost avoidance. RESULTS: The 48-hour decrease in corrected calcium was less in the bisphosphonate group than in the combination group (2.4 [1.6-3.4] vs 3.9 [3.5-5.3]; P < 0.001). However, initial calcium levels in the combination group were higher than in the bisphosphonate group, and calcium levels at 24, 48, and 72 hours were similar. Secondary outcomes did not differ. Average cost avoidance with bisphosphonate monotherapy was $11 248 per patient and $291 448 per year. CONCLUSIONS AND RELEVANCE: In the treatment of moderate to severe hypercalcemia of malignancy, IV bisphosphonate in combination with calcitonin resulted in a higher difference in corrected calcium levels at 48 hours compared with bisphosphonate therapy alone. However, corrected calcium levels in the first 72 hours, time to normocalcemia, and clinical outcomes were similar. The addition of calcitonin increases cost without substantial clinical benefit, and providers may consider avoiding calcitonin.

Sulfated alginate based complex for sustained calcitonin delivery and enhanced osteogenesis.

Direct administration of salmon calcitonin (sCT) by subcutaneous or intramuscular injection is limited by its low efficiency. Drug delivery systems with sustained delivery properties and high bioactivity are urgently needed. For clinical applications an economical and effective carrier is required, which has been a challenge until now. In this study, a simple alginate/alginate sulfate-sCT (Alg/AlgS-sCT) complex was successfully constructed for sustained release of sCT. The negatively charged sulfate groups facilitate bonding with sCT, which avoids the burst release of sCT and extends the release time up to 15 d (it is only 2 d for pure sCT). More importantly, the bioactivity of the released sCT is not affected during such a long release time, suggesting a conformation similar to that of native sCT.In vitroanalysis implies that the complex is biocompatible. Moreover, the combination of AlgS and sCT synergistically improves the osteogenic ability of MC3T3 cells, which show higher alkaline phosphatase levels and intracellular and extracellular calcium ion concentrations. The concentration of intracellular calcium ions is 5.26-fold higher than in the control group after 10 d of incubation. This simple yet effective system has potential applications in clinical trials and may inspire the design of other protein delivery systems.