Volume 4 · Number 1 · March 2012
- Gene study (OPG, RANKL, Runx2 and AGE receptors) in human osteoblast cultures from patients with type 2 diabetes mellitus and hip fracture. Influence of levels of glucose and AGEs [7-14]
- Cobb angle, vertebral deformity and fractures in alcoholic patients [15-21]
- Could the FRAX® index modify the treatment of osteoporosis? [23-26]
Osteoporosis and diabetes mellitus are two diseases with high prevalence which are associated with an increase in the risk of fragility fractures, and with a substantial impact on the morbidity and the mortality of the population in general. Although various observational studies have investigated the association between the two, the mechanism by which diabetes favours the appearance of fractures has not been properly established.
Most of the epidemiological studies carried out in patients with type 2 diabetes have shown an increase in bone mineral density1 in spite of which there is an increased risk of fracture of 1.5 for hip fracture, proximal humerus and distal radius2. In terms of the risk of vertebral fracture, the results are less uniform, although most of the studies also show an increase in risk3,4.
Hyperglycemia exerts both direct effects on bone cells, especially the osteoblasts, and indirect effects through the formation of products deriving from glycation.
In vitro, high levels of glycemia stimulate or inhibit osteoblast proliferation as a function of the phase of the cell cycle. The differentiation of these cells is especially suppressed, which is shown in the decrease in the production of osteocalcin, of the deposit of calcium and in bone mineralisation. The expression of the receptors for parathormone and vitamin D are also reduced. In addition, the hyperglycemia affects the functionality of the osteoblasts through the induction of an osmotic response mediated by its sensitivity to the acid medium induced by the lactate5.
Gene study (OPG, RANKL, Runx2 and AGE receptors) in human osteoblast cultures from patients with type 2 diabetes mellitus and hip fracture. Influence of levels of glucose and AGEs
Introduction: Diabetes mellitus (DM) type 2 is associated with a higher risk of osteoporotic fracture. Many factors have been indicated as possible mechanisms responsible for this, among which are changes in bone remodelling which may be induced by variations in circulating glucose or by the presence of non-oxidative advanced glycosylation end products (AGEs). The aim of this work has been to evaluate whether these variations generate changes in the expression of genes related to osteoblast differentiation and activity (OPG, RANKL, Runx2 and AGER) in primary cultures of human osteoblasts (hOB).
Material and methods: 12 patients were studied, belonging to three groups: 4 with osteoporotic fracture, 4 with osteoporotic fracture and DM type 2, and 4 patients with osteoarthritis, but who were not osteoporotic or diabetic (control group), with an average age of 80 ± 8, 84 ± 10 and 66 ± 11 years, respectively. Primary cultures of hOB from trabecular bone were carried out, to which were applied different stimuli over 24 hours. The gene study was carried out using real-time PCR.
Results: The genetic expression of RANKL was seen to increase in the diabetic group, although not to a significant degree, in the cultures which were high in glucose and high in glucose supplemented by AGEs (1.9 and 4.6 times higher vs control conditions; 2.3 and 4.4 times vs control group, respectively). The RANKL/OPG ratio stayed constant in the control group, however, in the diabetic group an increase was seen in all experimental conditions. In the case of Runx2 we found a significant increase in expression in the diabetic group with respect to the control group in the culture high in glucose and AGEs (OA = 1.08 ± 0.43; OP+DM = 3.33 ± 0.73; p = 0.039). No significant changes in the expression of OPG and AGER with respect to the control condition were observed for any of the culture conditions, in any of the patient groups.
Conclusions: The presence of a hyperglycaemic environment and AGEs alters the genetic expression of RANKL, of the RANKL/OPG ratio and Runx2 in osteoblast cultures from diabetic patients with hip fractures. These variations could generate changes in bone remodelling which could explain, at least partly, the lower bone resistance and the increase in the incidence of non-traumatic fractures in these patients.
Background: Hypercyphosis and vertebral deformity are related to vertebral fractures. There are no studies in chronic alcoholics.
Objective: To analyse the relationship which exists between the Cobb angle and different degrees of vertebral deformity, and bone mass and various variables related to bone metabolism in chronic alcoholic patients.
Material and methods: 57 alcoholic males aged 52 ± 12 years were included. The Cobb angle was calculated and the degree of vertebral deformity of T7, T8, T9 and T10 was measured using MorphoXpress® and thoracic X-ray. The bone mass in the spine and hip were determined using a DXA Hologic Walthan 2000, and exiting clinical fractures with the clinical history. In addition, the nutritional state, the degree of alcoholism, variables of hepatic function, the presence of hepatic cirrhosis, and bone metabolism, were analysed. The results were also studied in 20 controls of similar age and of the same sex.
Results: The patients had a greater Cobb angle in comparison with the controls ( 30 ± 9º vs 17 ± 5º, respectively, p<0.001). Those with cirrhosis had lower bone mass than those without in the lumbar vertebrae (p<0.01) and femoral neck (p=0.02). The deformities in T7, T8, T9 and T10 were associated with a greater cyphosis, longer period of consumption and with existing vertebral fractures (p<0.01), non-vertebral fractures (p<0.002) and hip fractures (p<0.001). There were 65 existing fractures, 46 in the rib, 12 vertebral and 7 in the hip. The patients with a higher Cobb angle had more vertebral (p<0.01) and non-vertebral (p=0.04) fractures, as well as a longer period of alcohol consumption (p=0.02).
Conclusions: Chronic alcoholics have greater cyphosis than the controls. Wedge or biconcave vertebral deformities are related with a greater cyphosis, higher consumption of alcohol and existing fractures. In this series a higher Cobb angle is related to existing vertebral fractures. The most intensive drinkers had a higher Cobb angle and more fractures.
Introduction: The FRAX® index is an algorithm devised by the WHO which, by evaluating risk factors, calculates the absolute risk of suffering any osteoporotic fracture or hip fracture in the subsequent 10 years. The aim of this work is to ascertain the risk of fracture in patients with suspected osteoporosis, using the FRAX® tool, and to ascertain how therapeutic decisions would be modified if these criteria were used.
Patients and method: The patients were drawn from a list of densitometries (DXA) carried out in the Hospital of Torrevieja during the first quarter of 2009. Using simple random sampling 110 women were selected, of whom 90 participated in this study. The FRAX® tool was applied to all of them, recording the treatment for osteoporosis which they were following, and the service which had initiated the prescription. A value of >10% for the principal fracture, and a value of 3% for a hip fracture, were considered to indicate a high risk of fracture.
Results: Fifteen patients (16.66%) had a FRAX® index with a high risk of fracture. Only 23% of patients in treatment had a FRAX® index with a high risk of fracture. 40% of those patients with a high risk FRAX® index were not taking any specific treatment.
Conclusions: The use of the FRAX® tool may change the indication for treatment in many patients in whom the decision had been based only on bone densitometry.
Background: In Spain, the flow of medical care for a patient with a fracture due to postmenopausal osteoporosis (PO) in the hospital system is not understood. A literature review has been carried out in order to define the hospital care pathway for patients with fracture due to PO in normal clinical practice, taking into account the different medical specialisms involved. In addition, it was attempted to determine the role of each specialist and the most common referral services.
Material and methods: The databases PubMed/Medline, ISI Web of Knowledge, EMBASE and Google Scholar; IBECS (Spanish Bibliographical Index in Health Sciences (Índice Bibliográfico Español en Ciencias de la Salud)) and MEDES (Medicine in Spanish (Medicina en Español)) were consulted, as well as the web pages of the Spanish Society of Rheumatology, the Spanish Society for Bone and Mineral Metabolism Research, the Spanish Society of Orthopaedic Surgery and Traumatology, and the Spanish Association for the Study of the Menopause, to identify publications appearing between 2000 and 2010 in English or Spanish. The principal national clinical practice guides (CPG) for PO were reviewed.
Results: A total of 114 articles were identified. After discounting non-relevant publications, duplicate publications and those published in languages other than English or Spanish, 13 articles were selected. 4 articles were excluded (n=2 screening for osteoporosis, n=1 risk factors, n=1 cost studies), with a total of 9 articles being reviewed. All the articles were international (n=9), including American (n=4), Canadian (n=2), Swiss (n=1), Irish (n=1) and multinational (n=1), and described the outpatient management of fractures due to PO mainly in the extra-hospital environment. Notable in this environment is the essential role of the orthopaedic surgeon and the need for their coordination with family doctors to guarantee the optimum follow up of patients and the prevention of second fractures. The CPGs reviewed referred only to the diagnosis and therapeutic management of the patient with PO. No information was found on referral services, or on the role of each specialist in the management of these patients.
Conclusions: The care pathway for patients with osteoporotic fracture, and which professionals are involved, are poorly described in the literature, both nationally and internationally. The clinical management of patients with fracture due to osteoporosis in hospitals is an area of healthcare which needs description and analysis.
Osteonecrosis of the jaw is a disease which needs to be taken into account whenever there is exposure of bone as a secondary result of any dental operation in a patient who has been taking biphosphonates over a long period of time. Unknown until the last few years, knowledge of such a pathology has increased due to the current increase in the taking of biphosphonates in the population, with most of the published cases being related to the taking of biphosphonates intravenously. We present 5 clinical cases of osteonecrosis of the jaw associated with the use of oral biphosphonates.
Annual cost of the drugs used in the treatment of osteoporosis after a review of the reference prices
In a review of the role of zoledronic acid in the treatment of osteoporosis published in a monograph of the Review of Osteoporosis and Mineral Metabolism 1 we included a table in which we presented the annual cost of the different drugs approved in Spain for the treatment of postmenopausal osteoporosis.
Subsequently, on the 30th December 2011, a resolution was published in the BOE due to which the reference prices of medicines were reviewed2, modifying downwards the prices of all drugs.