Idiopathic osteoporosis in men

Over the last decade, the increasingly significant problem of osteoporosis in men has begun to receive much more attention than in the past. In particular, recent observations from large scale population studies in males led to an advance in the understanding of morphologic basis of growth, maintenance and loss of bone in men, as well as new insights about the pathophysiology and treatment of this disorder. While fracture risk consistently increases after age 65 in men (with up to 50 % of cases due to secondary etiologies), osteoporosis and fractures may also occur in young or middle aged males in the absence of an identifiable etiology. For this category (so called idiopathic osteoporosis), there are still major gaps in knowledge, particularly concerning the etiology and the clinical management. This article provides a summary of recent developments in the acquisition and maintenance of bone strength in men, as well as new insights about the pathogenesis, diagnosis, and treatment of idiopathic osteoporosis

Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults With Chronic Hypoparathyroidism

Context: Reduced health-related quality of life (HRQoL) is common in patients with hypoparathyroidism on conventional therapy with calcium and active vitamin D supplements. Objective: To examine the effects of recombinant human parathyroid hormone (rhPTH[1-84]) on HRQoL as measured by the 36-Item Short Form Health Survey (SF-36) during the multinational, randomized, placebo-controlled REPLACE study. Patients: 122 adults with chronic hypoparathyroidism. Intervention(s): Following an optimization period when calcium and/or active vitamin D supplements were adjusted to reach target serum calcium levels (8.0-9.0 mg/dL; 2.0-2.2 mmol/L), patients were randomized to receive placebo (n=39) or rhPTH(1-84) (n=83) (starting dose 50 mug/day, could be titrated up to 100 mug/day); supplement doses were adjusted to maintain target serum calcium levels. Main Outcome Measure(s): Change from baseline (post-optimization, at randomization) to Week 24 in HRQoL as assessed by the SF-36v2 health survey. Results: Overall, the between-group differences were not statistically significant. However, in the rhPTH(1-84) group, there were significant improvements in the physical component summary score (P=0.004) and in body pain (P<0.05), general health (P<0.05), and vitality (P<0.001) domains as compared with baseline values. In the placebo group, there were no significant changes for any of the domains. The magnitude of change between 0 and 24 weeks in SF-36 scores was negatively correlated with baseline scores, such that patients with lower HRQoL at baseline were more likely to experience improvement in response to treatment. Conclusions: Treatment with rhPTH(1-84) may improve HRQoL in adults with hypoparathyroidism

Parathyroid adenoma apoplexy as a temporary solution of primary hyperparathyroidism: a case report

<p>Abstract</p> <p>Introduction</p> <p>The natural history of patients with spontaneous parathyroid necrosis is unknown. In this case report we describe the clinical course, laboratory, radiographic, bone densitometry tests, parathyroid ultrasonography and scintigraphy examinations of a patient performed over a period of eight years after she first presented with a sudden episode of spontaneous resolution of primary hyperparathyroidism (PHPT).</p> <p>Case presentation</p> <p>A 24-year-old woman with a clinical history and laboratory and radiographic tests compatible with PHPT suffered a sudden episode of cervical pain and presented with clinical evidence of hypocalcemia. Biopsy of a cervical nodule revealed necrotic material compatible with ischemia of the parathyroid. The follow-up of the patient presented four distinct phases: the first, which lasted two years, was compatible with a period of bone hunger during which it was necessary to introduce calcitriol and calcium carbonate. During this period, the patient showed bone mass gain. The second phase was characterized by normalization of calcium and parathyroid hormone levels and its end was difficult to define. During the third phase there was a recurrence of hypercalcemia associated with elevated parathyroid hormone (PTH) levels and loss of bone mass. The last phase corresponded to the interval after parathyroidectomy, which was characterized by normalization of serum levels of calcium and PTH, as well as bone mass gain.</p> <p>Conclusion</p> <p>This case report indicates that spontaneous resolution of PHPT by adenoma necrosis is potentially temporary. Thus, in cases in which a conservative approach is chosen, clinical and laboratory follow-up is indispensable. Bone mass measurement is a useful tool in the follow-up of these cases. However, this option exposes the patient to a potential roller-coaster ride of bone mass gain and loss, whose long term consequences are still unknown.</p

The first biosimilar approved for the treatment of osteoporosis

To demonstrate the clinical comparability between RGB-10 (a biosimilar teriparatide) and the originator, a comparative pharmacokinetic trial was conducted. The study was successful in establishing bioequivalence. Marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency in 2017.Teriparatide, the first bone anabolic agent, is the biologically active fragment of human parathyroid hormone. The imminent patent expiry of the originator will open the door for biosimilars to enter the osteology market, thereby improving access to a highly effective, yet prohibitively expensive therapy.Subsequent to establishing comparability on the quality and non-clinical levels between RGB-10, a biosimilar teriparatide, and its reference product (Forsteo®), a randomised, double-blind, 2-way cross-over comparative study (duration: four days) was conducted in 54 healthy women (ages: 18 to 55 years) to demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence and comparable safety of these products. Extents of exposure (AUC0-tlast) and peak exposure (Cmax), as measured by means of ELISA, were evaluated as co-primary PK endpoints, and serum calcium levels, as measured using standard automated techniques, were assessed for PD effects. Safety was monitored throughout the study.The 94.12% CIs for the ratio of the test to the reference treatments, used due to the two-stage design (85.20-98.60% and 85.51-99.52% for AUC0-tlast and Cmax, respectively), fell within the 80.00-125.00% acceptance range. The calcium PD parameters were essentially identical with geometric mean ratios (GMRs) of 99.93% and 99.87% for AUC and Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference.Based on the high level of similarity in the preclinical data and the results of this clinical study, marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency (EMA) in 2017

A Full Pharmacological Analysis of the Three Turkey β-Adrenoceptors and Comparison with the Human β-Adrenoceptors

There are three turkey β-adrenoceptors: the original turkey β-adrenoceptor from erythrocytes (tβtrunc, for which the X-ray crystal structure has recently been determined), tβ3C and tβ4C-receptors. This study examined the similarities and differences between these avian receptors and mammalian receptors with regards to binding characteristics and functional high and low affinity agonist conformations.Stable cell lines were constructed with each of the turkey β-adrenoceptors and 3H-CGP12177 whole cell binding, CRE-SPAP production and (3)H-cAMP accumulation assays performed. It was confirmed that the three turkey β-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey β-adrenoceptors to human β-adrenoceptors is between the turkey β3C-receptor and the human β2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the tβtrunc and tβ4C and the human β-adrenoceptors (e.g. with CGP20712A and ICI118551). The tβtrunc and tβ4C-adrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat β1-adrenoceptor and human β3-adrenoceptors. The tβ3C-receptor, similar to the human β2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.There are several similarities, but also several important differences, between the recently crystallised turkey β-adrenoceptor and the human β-adrenoceptors. These findings are important for those the field of drug discovery using the recently structural information from crystallised receptors to aid drug design. Furthermore, comparison of the amino-acid sequence for the turkey and human adrenoceptors may therefore shed more light on the residues involved in the existence of the secondary β-adrenoceptor conformation

Variation in plasma calcium analysis in primary care in Sweden - a multilevel analysis

<p>Abstract</p> <p>Background</p> <p>Primary hyperparathyroidism (pHPT) is a common disease that often remains undetected and causes severe disturbance especially in postmenopausal women. Therefore, national recommendations promoting early pHPT detection by plasma calcium (P-Ca) have been issued in Sweden. In this study we aimed to investigate variation of P-Ca analysis between physicians and health care centres (HCCs) in primary care in county of Skaraborg, Sweden.</p> <p>Methods</p> <p>In this cross sectional study of patients' records during 2005 we analysed records from 154 629 patients attending 457 physicians at 24 HCCs. We used multilevel logistic regression analysis (MLRA) and adjusted for patient, physician and HCC characteristics. Differences were expressed as median odds ratio (MOR).</p> <p>Results</p> <p>There was a substantial variation in number of P-Ca analyses between both HCCs (MOR_HCC1.65 [1.44-2.07]) and physicians (MOR_physician1.95 [1.85-2.08]). The odds for a P-Ca analysis were lower for male patients (OR 0.80 [0.77-0.83]) and increased with the number of diagnoses (OR 25.8 [23.5-28.5]). Sex of the physician had no influence on P-Ca test ordering (OR 0.93 [0.78-1.09]). Physicians under education ordered most P-Ca analyses (OR 1.69 [1.35-2.24]) and locum least (OR 0.73 [0.57-0.94]). More of the variance was attributed to the physician level than the HCC level. Different mix of patients did not explain this variance between physicians. Theoretically, if a patient were able to change both GP and HCC, the odds of a P-Ca analysis would in median increase by 2.45. Including characteristics of the patients, physicians and HCCs in the MLRA model did not explain the variance.</p> <p>Conclusions</p> <p>The physician level was more important than the HCC level for the variation in P-Ca analysis, but further exploration of unidentified contextual factors is crucial for future monitoring of practice variation.</p

Eucalcemic Parathyroid Hormone Elevation After Parathyroidectomy for Primary Sporadic Hyperparathyroidism: Risk Factors, Trend, and Outcome

BACKGROUND: Patients with eucalcemic parathyroid hormone elevation (ePTH) after parathyroidectomy for primary hyperparathyroidism (HPT) may be at risk of recurrence. We aimed to examine risk factors, trend of PTH level, and outcome of patients with ePTH 6 months after parathyroidectomy. METHODS: A total of 161 primary HPT were analyzed. The 6-month postoperative calcium and PTH levels were obtained. ePTH was defined as an elevated PTH level in the presence of normocalcemia. At 6 months, 98 had eucalcemic normal PTH and 63 (39.1%) had ePTH. Perioperative variables, PTH trend, and outcome were compared between 2 groups. Multivariable analyses were performed to identify independent preoperative and operative/postoperative risk factors for ePTH. RESULTS: Among preoperative factors, advanced age (odds ratio [OR] = 1.042, P = .027) and low 25-hydroxyvitamin D(3) (25OHD(3)) (OR = 1.043, P = .009) were independently associated with ePTH, whereas among operative/postoperative factors, high 10-min intraoperative PTH level (OR = 1.015, P = .040) and high postoperative 3-month PTH (OR = 1.048, P < .001) were independently associated with ePTH. After a mean follow-up of 38.7 months, recurrence rate was similar between the 2 groups (P = 1.00). In the first 2 postoperative years, 75 (46.6%) had ePTH on at least 1 occasion and 8 (5.0%) had persistently ePTH on every occasion. CONCLUSIONS: Advanced age, low 25OHD(3), high 10-min intraoperative PTH, and high postoperative 3-month PTH were independently associated with ePTH at 6-month. Although 39.1% of patients had ePTH at 6 months, more than 50% had at least 1 ePTH within the first 2 years of follow-up. Recurrence appeared similar between those with or without ePTH at 6 months.published_or_final_versionSpringer Open Choice, 21 Feb 201