Search

Background Hydroxyapatite (calcium and phosphate) spherules have been implicated in the initiation and establishment of age-related macular degeneration. Bisphosphonates could increase the dissolution of hydroxyapatite crystals and when they are used in elderly patients with osteoporosis they could reduce the risk of developing age-related macular degeneration. Objective To determine if oral bisphosphonate (BP) use is associated with the incidence of age-related macular degeneration in a large “real-world” population-based cohort of incident hip fracture patients. Design A cohort of 13,974 hip fracture patients (1999 to 2013) were used to conduct a: (a) propensity score matched cohort analysis and (b) nested case-control analysis. Setting A population-based study using electronic health records from UK primary care (Clinical Practice Research Datalink). Participants Hip fracture patients aged ≥50 years without age-related macular degeneration diagnosis prior to hip fracture date or in the first year of follow-up. Prior BP-users and those who died, transferred out or with last data collected before hip fracture were excluded. Exposures Incident BP use following hip fracture. BP use was further categorised according to medication possession ratio in quartiles. Main outcome measures Primary outcome was a diagnosis of age-related macular degeneration after the first year from index date. Propensity scores were used to match 1:1 BP-users to non-BP users. Covariates in the propensity score were index year, age, gender, body mass index, smoking, alcohol drinking, region, drug confounders and comorbidities. Subhazard ratios and their 95% confidence intervals were calculated including death as a competing risk. A nested 1:20 case-control analysis using conditional logistic regression provided risk estimates according to medication possession ratio. Results Among 6,208 matched patients and during 22,142 person-years of follow-up, 57 (1.8%) and 42 (1.4%) age-related macular degeneration cases occurred in BP-users and non-BP users, respectively. The survival analysis model did not provide significant evidence of a higher risk of AMD in BP-users (subhazard ratio: 1.60; CI: 0.95-2.72; P=0.08) although there was a significant increased risk among BP-users with high medication possession ratio (top quartile) relative to non-BP users (odds ratio: 5.08, 3.11-8.30; P Conclusions Overall, oral BP use was not associated with an increased risk of age-related macular degeneration in this cohort of hip fracture patients, although the risk increased significantly with higher medication possession ratio. More data are needed to confirm these findings.

Objective: To investigate the association between oral bisphosphonate (BP) use and the risk of developing age-related macular degeneration (AMD).

Tuberculosis accounts for 0.5-1.0% of primary renal diagnoses among patients with end-stage renal disease reported to the EDTA Registry. In 1991, Greece was the country with the highest incidence (4.51%) among new patients taken on for dialysis/transplantation, followed by Portugal (2.03%). Some countries have reported not a single case of renal failure as a result of tuberculosis. We believe that the incidence of tuberculosis may have been seriously underestimated, since the tubulointerstitial form of tuberculosis, as opposed to the classical form, can easily be overlooked. There could also be patients classified under other EDTA diagnostic codes. Furthermore, in the EDTA database certain categories of renal diagnosis (00, 10, 20, 30) covering almost 40% of the whole renal population, have deliberately broad usage. Therefore, it is possible that some of the individuals allocated to these groups could have tuberculosis as primary renal diagnosis. We have no direct evidence to support this claim but our study of patients with end-stage renal disease suggests that patients with presumed glomerulonephritis behave differently from the well defined group of patients with biopsy proven glomerulonephritis, as regards evolution of renal bone disease. As a treatable form of progressive renal failure it is clearly important to identify individual cases. Therefore, renal biopsy should always be considered in patients with equal smooth kidneys radiologically, whose renal diagnosis is unknown and who come from an 'at risk' population as variation in the incidence of tuberculosis between racial groups is well established.

Calcitonin is a 32-amino acid circulating hormone involved in skeletal homeostasis. Its primary target cell is the osteoclast, the bone-resorbing cell. Low picomolar concentrations of calcitonin inhibit bone resorption and produce a characteristic morphological change in isolated osteoclasts. The latter change has been separated biophysically into quiescence (Q) and retraction (R) components. Both components are involved in the inhibition of bone resorption, but are nevertheless distinct. The Q effect is mediated by a cholera toxin-sensitive Gs-like G protein involving a cyclic AMP-dependent pathway. The R effect is triggered by a rise of cytosolic [Ca2+] and probably involves the activation of a pertussis toxin-sensitive Gq-like G protein. The parallel activation pathways appear to be coupled proximally to separate calcitonin receptor subtypes. One of these cross-reacts with calcitonin and its related peptides, amylin and calcitonin gene-related peptide, while the other appears highly calcitonin-specific. However, in the renal epithelial cells, there is evidence for differential coupling of a single receptor to more than one transduction pathway. This occurs in a cell cycle-dependent manner. Two members of the calcitonin receptor family, the porcine renal receptor and the human ovarian receptor, have been cloned and sequenced. Both are of a high affinity (nM) and are functionally coupled to increases in intracellular cyclic AMP. The recombinant porcine renal calcitonin receptor also displays coupling to the phospholipase C-IP3 system. Both receptors show little (30%), indicating that the receptors for these hormones represent a new family of G protein-coupled receptors with unique structural and functional properties. © 1998 Elsevier B.V. All rights reserved.

In a retrospective study, we have assessed the efficacy of oral calcitriol on the evolution of hyperparathyroid bone disease in patients on hemodialysis. 33 patients who had received calcitriol for at least one year and up to 7 years were carefully matched with controls for gender, years on hemodialysis and severity of radiological hyperparathyroidism both at the start of haemodialysis and at the start of the study. Young patients (

Bone resorption appears to be dependent on a range of processes. It requires an adequate number of osteoclasts to access bone mineral. These osteoclasts must be activated by a mechanism which is dependent upon prior osteoblastic stimulation. A range of factors then contribute to the formation of a functionally effective resorptive hemivacuole. These entail osteoclast adhesion to the bone surface leading to the formation of a sealing zone. Only then can subsequent processes such as H+ ion transport, enzyme secretion and matrix digestion become effective. Thus, any one process is potentially limiting to resorption and is a potential target for regulation. Long-range regulation takes place through the action of hormones, of which the mode of action of calcitonin has been the subject of recent investigations in isolated osteoclasts. Such studies have shown a possible involvement of distinguishable receptor subtypes, the occupancy of which may activate at least two types of triggering mechanism. It is likely that an eventual influence on motility properties through G protein mediation accounts for the actions of this hormone and of related peptides such as amylin and CGRP at the cellular level. Similar pathways may contribute to shorter range modulation of osteoclast activity by increases in ambient Ca2+. Finally, there is recent evidence for a contribution of endothelial cell-derived product to osteoclast regulation.