Transdermal Delivery of Salmon Calcitonin Using a Dissolving Microneedle Array: Characterization, Stability, and In vivo Pharmacodynamics.

Salmon calcitonin (sCT) is a polypeptide drug, possessing the ability to inhibit osteoclast-mediated bone resorption. Just like other bioactive macromolecules, sCT is generally administered to the patients by either injection for poor compliance or through nasal spray for low bioavailability, which limits its use as therapeutic drugs. In the present study, to overcome the limitations of the conventional routes, two new dissolving microneedle arrays (DMNAs) based on transdermal sCT delivery systems were developed, namely sCT-DMNA-1 (sCT/Dex/K90E) and sCT-DMNA-2 (sCT/Dex-Tre/K90E) with the same dimension, meeting the requirements of suitable mechanical properties. An accurate and reliable method was established to determine the needle drug loading proportion in sCT-DMNAs. The stability study exhibited that the addition of trehalose could improve the stability of sCT in DMNA under high temperature and humidity. Further, in vivo pharmacodynamic study revealed that DMNA patch could significantly enhanced relative bioavailability to approximately 70%, and the addition of trehalose was found to be beneficial for sCT transdermal delivery. Therefore, sCT-DMNA is expected to replace traditional dosage form, providing a secure, efficient, and low-pain therapeutic strategy for bone disorders.

Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice.

RATIONALE: Amylin receptors consist of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs). The identification of amylin receptors in areas processing reward, namely laterodorsal tegmental area (LDTg), ventral tegmental area (VTA), and nucleus accumbens (NAc), has attributed them a role as reward regulators. Indeed, acute activation of amylin receptors by the amylin receptor agonist salmon calcitonin (sCT) attenuates alcohol-induced behaviours in rodents. OBJECTIVES: The effects of long-term administration of sCT on alcohol-related behaviours and the molecular mechanisms underlying these processes are not yet elucidated. To fill this knowledge gap, we investigated the effects of sub-chronic sCT treatment on the locomotor stimulatory responses to alcohol in mice and the molecular pathways involved. METHODS: We assessed the behavioural effects of sub-chronic sCT treatment by means of locomotor activity experiments in mice. We used western blot to identify changes of the CTR levels and ex vivo biochemical analysis to detect changes in monoamines and their metabolites. RESULTS: After discontinuation for 5 days of sCT treatment, alcohol did not induce locomotor stimulation in mice pre-treated with sCT when compared with vehicle, without altering secondary behavioural parameters of the locomotor activity experiment or the protein levels of the CTR in reward-related areas in the same set of animals. Moreover, repeated sCT treatment altered monoaminergic neurotransmission in various brain areas, including increased serotonin and decreased dopamine turnover in the VTA. Lastly, we identified a differential effect of repeated sCT and acute alcohol administration on alcohol-induced locomotion in mice, where sCT initially attenuated and later increased this alcohol response. It was further found that this treatment combination did not affect secondary behavioural parameters measured in this locomotor activity experiments. CONCLUSIONS: These data suggest that sub-chronic sCT treatment differentially alters the ability of alcohol to cause locomotor stimulation, possibly through molecular mechanisms involving various neurotransmitter systems and not the CTR levels per se.

Successful treatment for bilateral femoral neck insufficiency fractures: a rare lesion case report and an updated review of the literature.

BACKGROUND: The incidence of insufficiency fracture (IF) at femoral neck is low, accounting for about 5% of all insufficiency fractures, and IF at bilateral femoral neck is less common with more occurrence in athlete or serviceman. With the aging of populations, more cases of bilateral femoral neck IF have occurred recently, while the standard clinical treatment still remains lacking due to the complexity of these patients. CASE PRESENTATION: A 55-year-old male patient complained pain in his bilateral hip, with no history of trauma, glucocorticoid hormone consumption or radiotherapy, and imaging examination revealed fracture nonunion and shortening in his left femoral neck, and double fracture line on the right femoral neck. The patient received a cementless THA for the left femoral neck fracture and conservative treatment for the right side, followed by Elcatonin injection and oral administration of Carbonate D3 Granules. After 4 months of fellow-up, the patient presented improved functional scorings in bilateral hip joints, with no signs of prothesis infection or loosening. CONCLUSION: We present a rare case of bilateral femoral neck IF in a middle-aged male and the treatment is successful. The timely CT and MRI examinations of bilateral hip joints for patients was necessary for orthopedists to select proper therapeutic regimen. In addition, the choice for therapeutic regimen of bilateral femoral IF should not only be based on the professional judgement of orthopedists, but also on the wishes of patients.

Efficacy of SPM-NONOate following intrapulmonary delivery in promoting absorptions of poorly absorbed macromolecules in rats and the underling mechanism.

This research aims to investigate the potential of N-[4-[1-(3-Aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl]-1,3-propanediamine (SPM-NONOate) for promoting the absorption of poorly absorbed macromolecules delivered by intrapulmonary route. Influence of SPM-NONOate on the drug absorption was characterized by using a series of fluorescein isothiocyanate-labeled dextrans (FDs) as affordable models of hydrophilic macromolecules with established tools for quantitative analysis. SPM-NONOate increased concentration-dependently within 1-10 mM the pulmonary absorptions of FDs in rats. Moreover, this promoting effect varied with the molecular weight of FDs, and the largest absorption enhancement effect was obtained for FD70. SPM-NONOate also showed promising enhancement potential on the absorption of some therapeutic peptides, where obvious hypoglycemic and hypocalcemic effects were observed after intrapulmonary delivery of insulin and calcitionin, respectively, with SPM-NONOate to rats. The safety of SPM-NONOate was confirmed based on measurement of some biological markers in bronchoalveolar lavage fluid (BALF) of rats. Additionally, mechanism underling the absorption enhancement action of SPM-NONOate was explored by combinatorial administration of FD4 and SPM-NONOate with various scavengers and generator to rat lungs. Results indicated that NO released from SPM-NONOate induced the enhancement in the drug absorption, and peroxynitrate, a NO metabolite, possibly participated in the absorption enhancing action of SPM-NONOate.

An aneurysmal bone cyst at T1 treated with bone grafts containing calcitonin and methylprednisolone.

Aneurysmal bone cysts (ABCs) rarely trigger pathological fractures. Various surgical and nonsurgical treatments have been reported for this condition. Herein, we present the examination findings and treatment for a 15-year-old girl who initially presented with adolescent idiopathic scoliosis and mild back pain, but subsequently experienced severe back pain. Magnetic resonance imaging revealed an ABC at T1, with an associated pathological fracture. We successfully treated the patient using posterior fixation with instrumentation, curettage, and bone grafts combined with calcitonin and methylprednisolone (mPSL). At 3 years post-surgery, there was no ABC recurrence and only mild back pain persisted. To our knowledge, this is the first report of open surgery (curettage and fixation) with local intralesional administration of calcitonin and mPSL for an ABC-induced pathological spinal fracture. We believe that this treatment is an effective option for ABCs associated with a pathological spinal fracture.

An amylin analogue attenuates alcohol-related behaviours in various animal models of alcohol use disorder.

Recent findings have identified salmon calcitonin (sCT), an amylin receptor agonist and analogue of endogenous amylin, as a potential regulator of alcohol-induced activation of the mesolimbic dopamine system and alcohol consumption. Providing that the role of amylin signalling in alcohol-related behaviours remains unknown, the present experiments investigate the effect of sCT on these behaviours and the mechanisms involved. We showed that repeated sCT administration decreased alcohol and food intake in outbred rats. Moreover, single administration of the potent amylin receptor antagonist, AC187, increased short-term alcohol intake in outbred alcohol-consuming rats, but did not affect food intake. Acute administration of sCT prevented relapse-like drinking in the "alcohol deprivation effect" model in outbred alcohol-experienced rats. Additionally, acute sCT administration reduced operant oral alcohol self-administration (under the fixed ratio 4 schedule of reinforcement) in selectively bred Sardinian alcohol-preferring rats, while it did not alter operant self-administration (under the progressive ratio schedule of reinforcement) of a highly palatable chocolate-flavoured beverage in outbred rats. Lastly, we identified differential amylin receptor expression in high compared to low alcohol-consuming rats, as reflected by decreased calcitonin receptor and increased receptor activity modifying protein 1 expression in the nucleus accumbens (NAc) of high consumers. Collectively, our data suggest that amylin signalling, especially in the NAc, may contribute to reduction of various alcohol-related behaviours.

Calcitonin Stewardship Strategies.

Despite being approved by the Food and Drug Administration for over 30 years, calcitonin salmon has seen a dramatic increase in acquisition cost over the last few years. Being commonly used for the treatment of hypercalcemia of malignancy, health systems must implement stewardship strategies in order to curtail usage. This review is intended to provide a background on calcitonin usage for hypercalcemia of malignancy and associated strategies to ensure appropriateness of utilization within health systems.

Calcitonin as an anticalcification treatment for implantable biological tissues.

BACKGROUND AND AIM OF THE STUDY: Calcification remains the major role of failure of implantable biomedical material and in particular of bioprosthetic valves. Various treatments have been proposed to mitigate calcification of glutaraldehyde-fixed bioprosthetic valves but none have succeeded in inhibiting or mitigating efficiently the calcification process of the implantable biological tissues. Since the discovery of calcitonin (CT) and its therapeutic role in treating hypercalcemic patients, CT has never been tried as an anticalcification treatment for biomaterials. It is postulated, that tissue calcification may be efficiently minimized by forming adducts with aldehyde groups thus eliminating the places of the biological tissues onto the calcium cations could be deposited. MATERIAL AND METHODS: Fresh porcine aortic leaflets were cut radially in three parts. Three groups of tissue were created. Group I (glutaraldehyde only), Group II (glutaraldehyde with 1% CT) and Group III (glutaraldehyde with 10% CT). All tissues were then implanted subdermally in three sets of 8 (Group I) and 9 (Group II and Group III) male Wistar rats of 12 days old. 21 days later the rats were euthanized by inhalation of CO2. The tissues were retrieved and after rinsing with distilled water 3 times, were lyophilized at -40°C at high vacuum pressure of approximately 100mmHg for 16h. The calcium content was then measured with flat atomic absorption technique. RESULTS: The preimplantation values of Ca concentration as expressed in mg Ca/g of tissue were 1.79±0.14 in Group I, 4.78±0.0079 in Group II and 2.88±0.17 in Group III (p=ns). 21 days later the values of Ca concentration were 126.95±12.97 for Group I, 24.69±2.71 for Group II (p<0.05) and 27.16±2.95 for Group III (p<0.05). There was not significance difference between Groups II and III, even if Group II showed a less accumulation of Ca concentration (×5.16) than Group III (×9.43). CONCLUSION: An anticalcification treatment based on calcitonin as an additive to buffered glutaraldehyde, mitigates the calcification process of the implantable biological tissues, as compared to glutaraldehyde treatment only.

Caso clínico: hipofosfatasia de la niñez. Seguimiento clínico / Clinical case: childhood hypophosphatasia. Clinical follow-up

La hipofosfatasia (HP) es una enfermedad congénita, causada por mutaciones con pérdida de función en el gen ALPL que codifica la isoenzima no específica de tejido de la fosfatasa alcalina (TNSALP). Su expresión clínica es muy variable, desde casos de muerte intraútero por alteración grave de la mineralización ósea, hasta casos solo con caída prematura de la dentición. Se presenta el caso clínico de un varón al que se le diagnosticó odontohipofosfatasia a los 30 meses por pérdida temprana de piezas dentarias y niveles anormalmente bajos de fosfatasa alcalina, sin signos de raquitismo ni deformidades óseas. Durante su seguimiento, hasta los 13 años, presentó síntomas compatibles con HP infantil leve, como cansancio al caminar, incoordinación en la marcha y dolor en miembros inferiores que aumentaban con la actividad física. Ante la aparición de edema bimaleolar y poca respuesta al tratamiento con calcitonina y antiinflamatorios, se descartaron patologías infecciosas o reumáticas o ambas y se diagnosticó, por biopsia de tibia y peroné, periostitis sin detección de cristales de pirofosfato. Los controles radiológicos durante su evolución mostraron ensanchamiento metafisario en muñeca, falta de remodelado de metacarpianos, hojaldrado perióstico en tibia y peroné e hipomineralización en metáfisis tibiales, con "lenguas radiolúcidas" características de HP. Como conclusión, la hipofosfatasia debe considerarse como una entidad clínica para descartar en niños que presentan pérdida temprana de dientes. La presencia de este cuadro clínico es en general suficiente para realizar el diagnóstico de HP de la niñez. (AU)

Hypophosphatasia (HP) is a congenital disease, caused by mutations with loss of function in the gene ALPL that encodes the non-specific tissue isoenzyme of alkaline phosphatase (TNSALP). Its clinical expression displays considerable variability, from cases of intrauterine death due to severe alteration of bone mineralization, to cases with only early loss of teeth. We report the case of a male, diagnosed as odontohypophosphatasia at 30 months of age due to early loss of teeth and abnormally low levels of alkaline phosphatase, without signs of rickets or bone deformities. During follow-up, up to 13 years of age, he presented symptoms consistent with mild infantile HP such as tiredness when walking, lack of gait coordination, and pain in lower limbs, especially after physical activity. Due to the appearance of bimalleolar edema and poor response to treatment with calcitonin and anti-inflammatory drugs, infectious and / or rheumatic pathologies were ruled out. Periostitis without pyrophosphate crystal detection was diagnosed by tibial and fibular biopsy. Radiological controls during follow up showed metaphyseal wrist enlargement, lack of remodeling of metacarpals, periosteal flaking in the tibia and fibula and hypomineralization in the tibial metaphysis, with "radiolucent tongues"; characteristic of HP. In conclusion, hypophosphatasia should be considered as a clinical entity in children who present early loss of teeth. The presentation of this clinical case is generally sufficient to make the diagnosis of childhood HP. (AU)

Comparative risks for cancer associated with use of calcitonin, bisphosphonates or selective estrogen receptor modulators among osteoporosis patients: a population-based cohort study.

BACKGROUND: This population-based cohort study was to compare the risks of incident cancer in osteoporosis patients who used bisphosphonates, calcitonin or selective estrogen receptor modulators (SERMs). METHODS: We identified 9995 patients who were diagnosed with osteoporosis and prescribed osteoporosis drugs (bisphosphonate (n = 4675), calcitonin (n = 3993) and SERMs (n = 1327)) between 1 January 2000 and 31 December 2006 in Taiwan's National Health Insurance Research Database. Date of first prescription of osteoporosis drugs was assigned as the index date. The outcome measurement was incident cancer, defined by a first-ever inpatient visit with a primary diagnosis of cancer. All patients were followed until the occurrence of cancer. For those who did not develop cancer, we censored them at 1 year after their last prescription of osteoporosis drugs. Cox proportional hazard models were used to examine the association between risk of cancer and use of calcitonin, bisphosphonates or SERMs. RESULTS: The incidence rate of cancer was 68.8, 34.0 and 29.6 per 1000 person years in the calcitonin, SERMs and bisphosphonate cohorts, respectively. Compared with bisphosphonate users, calcitonin users were associated with an increased risk of cancer (adjusted hazard ratio (HR) 2.11, 95% confidence interval (CI) 2.01-2.21, P < 0.001). SERM users were associated with an increased risk of cancer (adjusted HR 1.20, 95% CI 1.13-1.28, P < 0.001). CONCLUSION: Our findings suggest that calcitonin is associated with an increased risk of cancer than bisphosphonate, supporting the recent warning issued by the European Medicines Agency and US Food and Drug Administration. SERMs is found to be associated with an increased risk of cancer than bisphosphonate.

Supramolecular nanoparticles of calcitonin and dipeptide for long-term controlled release.

Salmon calcitonin (sCT) is a therapeutic polypeptide drug widely used to treat bone diseases such as osteoporosis (more than 200 million patients all over the world). The half-life of sCT is very short (~1h), thus various delivery systems have been developed for sCT in order to avoid frequent injections. However, most delivery systems use polymeric materials, which may limit their applications in clinic formulations due to the biocompatibility issue. We observed that a very simple dipeptide (Asp-Phe, DF) was co-assembled with sCT into supramolecular nanoparticles. These nanoparticles can significantly prolong the acting time of sCT to beyond one month after just a single subcutaneous injection. The assembling and releasing mechanisms were thoroughly investigated by both in vitro and in vivo methods, as well as by molecular dynamics simulations. This work provides an alternative strategy of designing protein/peptide drug delivery systems with long-lasting therapeutic effects.

The Preventive Value of Epidural Calcitonin in Patients with Lower Limb Amputation.

BACKGROUND: Postamputation pain is highly prevalent after limb amputation with neuropathic nature; calcitonin may effectively relieve many neuropathic pain states. DESIGN: Double-blind randomized multicenter study. SETTING: Our study hypothesis is to evaluate the preventive value of epidural calcitonin on postoperative pain, grade of phantom pain, and the development of allodynia and hyperalgesia in patients undergoing lower limb amputation. PATIENTS: A cohort of 60 diabetic patients of both genders suffering from vascular insufficiency of one or both lower limbs underwent minor or major lower limb amputation. Patients were divided randomly into two equal groups: an epidural bupivacaine-calcitonin-fentanyl (BCF) group and a bupivacaine-fentanyl (BF) group. METHODS: Patients were instructed about the use of a 10 cm visual analog scale (VAS). Phantom limb pain was graded using a four-grade scale. Pin-prick hyperalgesia and allodynia were evaluated at one week, one month, three months, and six months after surgery. RESULTS: There were no significant differences between groups regarding patients' characteristics. There was no significant difference in the VAS scale between groups. There was statically significant improvement in the grade of phantom pain in the BCF group at six and 12 months after surgery ( P = 0.033 and 0.001, respectively). A significantly higher number of patients developed allodynia in the BF group at six ( P = 0.039) and 12 ( P = 0.013) months and hyperalgesia at 12 months ( P = 0.025). CONCLUSION: The preventive use of epidural calcitonin improved the grade of phantom pain and reduced the incidence of allodynia and hyperalgesia in patients undergoing lower limb amputation under combined spinal-epidural anesthesia during one year of follow-up.

Treatment of aneurysmal bone cysts by percutaneous CT-guided injection of calcitonin and steroid.

OBJECTIVES: To determine the efficacy and safety of percutaneous calcitonin and steroid injection in the treatment of aneurysmal bone cysts (ABCs). MATERIALS AND METHODS: Our study was IRB-approved and HIPAA-compliant. We reviewed pre- and post-procedural imaging studies and medical records of all CT-guided percutaneous injections of ABCs with calcitonin and steroid performed at our institution between 2003 and 2015. RESULTS: Treatment success based on imaging was categorized as substantial (51-100 %), partial (1-50 %), or none (0 %) by comparing radiographs of the lesion before and after treatment. Our study group comprised 9 patients (7 female, 2 male; mean age 19 ± 5 (range 12-25) years). ABCs were located in the pubis (n = 3), femur (n = 2), and humerus/scapula/ilium/sacrum (n = 1 for each). One patient did not have any clinical or imaging follow-up. For the other 8 patients, clinical and imaging follow-up ranged from 1 to 93 months (mean 16 ± 29 months). One patient had two injections, and 1 patient had three injections. Six out of eight patients (75 %) had complete symptomatic relief and 2 patients (25 %) had partial symptomatic relief after initial injection. Imaging follow-up revealed substantial imaging response in 4 out of 8 patients (50 %). There was a partial imaging response in 2 patients (25 %) and no imaging response in 2 out of 8 patients (25 %), and all 4 of these patients had local recurrence. There were no complications. CONCLUSION: Percutaneous CT-guided injection of ABCs with calcitonin and steroid is a safe and effective treatment. Lack of imaging response may necessitate more aggressive treatment to minimize local recurrence.

Hyperparathyroidism-jaw Tumor Syndrome: An Overlooked Cause of Severe Hypercalcemia.

Ossifying fibromas of the maxillofacial bones are an uncommon form of benign neoplasm usually treated by surgical excision. Up to 30% of patients with hyperparathyroidism-jaw tumor syndrome, a rare form of multiple endocrine neoplasia resulting from autosomal dominant inactivating mutation of the Hrpt2 tumor suppressor gene, initially present with ossifying fibromas. Coincident hypercalcemia because of the presence of parathyroid adenoma is common in these patients, of whom 15% may have or may develop parathyroid carcinoma. The authors present a case of severe postsurgical hypercalcemia after removal of a large maxillary ossifying fibroma in a patient with previously unrecognized hyperparathyroidism-jaw tumor AU3 syndrome.

Advances in Controlled Drug Delivery for Treatment of Osteoporosis.

Osteoporosis, which is characterized by resorption of bone exceeding formation, remains a significant human health concern, and the impact of this condition will only increase with the "graying" of the worldwide population. This review focuses on current and emerging approaches for delivering therapeutic agents to restore bone remodeling homeostasis. Well-known antiresorptive and anabolic agents, such as estrogen, estrogen analogs, bisphosphonates, calcitonin, and parathyroid hormone, along with newer modulators and antibodies, are primarily administered orally, intravenously, or subcutaneously. Although these treatments can be effective, continuing problems include patient noncompliance and adverse systemic or remote-site effects. Controlled drug delivery via polymeric, targeted, and active release systems extends drug half-life by shielding against premature degradation and improves bioavailability while also providing prolonged, sustained, or intermittent release at therapeutic doses to more effectively treat osteoporosis and associated fracture risk.

Coated minispheres of salmon calcitonin target rat intestinal regions to achieve systemic bioavailability: Comparison between intestinal instillation and oral gavage.

Achieving oral peptide delivery is an elusive challenge. Emulsion-based minispheres of salmon calcitonin (sCT) were synthesized using single multiple pill (SmPill®) technology incorporating the permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10), or coco-glucoside (CG), or the pH acidifier, citric acid (CA). Minispheres were coated with an outer layer of Eudragit® L30 D-55 (designed for jejunal release) or Surelease®/Pectin (designed for colonic release). The process was mild and in vitro biological activity of sCT was retained upon release from minispheres stored up to 4months. In vitro release profiles suggested that sCT was released from minispheres by diffusion through coatings due to swelling of gelatin and the polymeric matrix upon contact with PBS at pH6.8. X-ray analysis confirmed that coated minispheres dissolved at the intended intestinal region of rats following oral gavage. Uncoated minispheres at a dose of ~2000I.U.sCT/kg were administered to rats by intra-jejunal (i.j.) or intra-colonic (i.c.) instillation and caused hypocalcaemia. Notable sCT absolute bioavailability (F) values were: 5.5% from minispheres containing NaTDC (i.j), 17.3% with CG (i.c.) and 18.2% with C10 (i.c.). Coated minispheres administered by oral gavage at threefold higher doses also induced hypocalcaemia. A highly competitive F value of 2.7% was obtained for orally-administered sCT-minispheres containing CG (45µmol/kg) and coated with Eudragit®. In conclusion, the SmPill® technology is a potential dosage form for several peptides when formulated with PEs and coated for regional delivery. PK data from instillations over-estimates oral bioavailability and poorly predicts rank ordering of formulations.

Calcitonin effects on shoulder adhesive capsulitis.

INTRODUCTION: Adhesive capsulitis (frozen shoulder) is a relatively prevalent disease of shoulder and affects soft tissue of glenohumeral joint. Signs include painful restricted motion and disability of the patient in daily activities. Calcitonin is a thyroid hormone, and its effectiveness has been demonstrated in painful conditions. The presents study aims to evaluate the effect of calcitonin in treating shoulder adhesive capsulitis. METHOD: This double-blinded randomized clinical trial was conducted on 64 patients suffering from shoulder adhesive capsulitis. The intervention and control groups were given intranasal calcitonin and placebo for 6 weeks, respectively. For both groups, physiotherapy and non-steroidal anti-inflammatory drugs were administered correspondingly. The patients were evaluated pre- and post-treatment for shoulder pain and shoulder range of motion (ROM). Shoulder functional outcome (secondary outcome) was evaluated using Disability of Arm, Shoulder, and Hand, Shoulder Pain and Disability Index, and Health Assessment Questionnaire disability criteria. RESULTS: The mean age of patients in calcitonin and control group was 52.4 ± 4.6 and 53.2 ± 4.9, respectively. Demographic characteristics and pre-treatment scores were similar in both groups (all P > 0.05). In post-treatment follow-up, shoulder pain, ROM, and the patients' functional scores were significantly improved in both groups (P < 0.001); however, the improvement in calcitonin group was more effective than that of placebo group. CONCLUSION: Intranasal calcitonin spray could be an additional safe alternative in shoulder adhesive capsulitis with regard to the efficiency in alleviating pain and improving functional outcome. LEVEL OF EVIDENCE: II.

Pharmacodynamics and pharmacokinetics of oral salmon calcitonin in the treatment of osteoporosis.

INTRODUCTION: Salmon calcitonin (sCT) has been used for the treatment of postmenopausal osteoporosis for over 30 years. It is available in injectable and intranasal formulations. Two oral formulations have recently been developed. AREAS COVERED: The basis for oral sCT's bioavailability rests with a carrier molecule (8-(N-2-hydroxy-5-chloro-benzoyl)-amino-caprylic acid) or an acid-resistant enteric coating (Eudragit® polymer containing citric acid). With these formulations, sCT is resistant to gastric acid, and thus becomes available for absorption at the higher pH of the small intestine. Even though the changes in bone mineral density and bone turnover markers are greater with oral compared to nasal sCT, it shows only minor effects on these surrogate markers. EXPERT OPINION: Oral sCT is attractive in concept as it is would be more convenient to patients than other routes of administration. While there may be other advantages to the oral formulation such as improving bone mineral density to a greater extent than nasal CT, anti-fracture efficacy has not been shown in a recent major clinical trial. Together with the possibility of an association between the drug and cancer and the availability of antiresorptive drug classes that are clearly more efficacious than sCT, successful development of oral sCT as a treatment for postmenopausal osteoporosis is uncertain.

Can calcitonin nasal spray reduce the risk of recurrence of central giant cell granuloma of the jaws? A double-blind clinical trial.

Recurrence is a major problem following the treatment of aggressive central giant cell granuloma (CGCG). The aim of this study was to compare the frequency of recurrence between patients who received calcitonin nasal spray after curettage of CGCGs and those who did not. A double-blind clinical trial was designed. Patients were allocated to one of two groups: those in the calcitonin group underwent curettage and received calcitonin salmon nasal spray 200IU/day once a day for 3 months after surgery; those in the control group underwent curettage of CGCGs and received a placebo once a day for 3 months after surgery. All patients were followed for 5 years after surgery. Twenty-four patients were treated in the two groups. There was no difference in age, sex, tumour size, or tumour location between the two groups (P>0.05). Eight of the 24 patients (33.3%) had recurrences during the follow-up period: one in the calcitonin group (9.1%) and seven in the control group (53.8%). Analysis of the data demonstrated a significant difference between the two study groups (P=0.033). It appears that calcitonin nasal spray may reduce the frequency of recurrence in aggressive CGCGs in the mandible and maxilla.