Recent Advances in Osteoporosis

SE-2-1

Osteoporosis in Renal Failure: To Treat or not to Treat?

ManJu CHandran

Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, DUKENUS Graduate Medical School Chapter of Endocrinology, College of Medicine, Singapore Immediate Past President, Endocrine and Metabolic Society of Singapore (EMSS)

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Practically speaking, osteoporosis is diagnosed by one of two ways: a low trauma fracture which is unexplained by any other cause of bone fragility or when there is a reduction in bone quantity as measured by BMD by dual energy X-ray absorptiometry (DXA). The diagnosis of osteoporosis in Chronic Kidney Disease (CKD) however is fraught with uncertainties. Patients with CKD could have alternations in bone quality due to increased or decreased bone turnover, impaired mineralization, or a combination of these and/or decreases in BMD. This means that techniques, such as BMD testing, to evaluate fracture risk due to osteoporosis may not be as useful in patients with CKD as they are in the general population. Patients with CKD-MBD may have one of 4 metabolic bone diseaSE- High turnover bone disease (Osteitis Fibrosa Cystica), Low turnover bone disease (Adynamic bone disease), Mixed Osteodystophy, and Osteomalacia. The differentiation between these bone diseases is not simple and straightforward and can conclusively be done only by bone biopsy and histomorphometry. In addition to and independent of alterations in bone quality and quantity, CKD patients are more likely to fracture, because they are at an increased risk for falls from muscle weakness and impaired balance secondary to poor nutrition, inactivity, myopathy, and peripheral neuropathy. The treatment of osteoporosis in CKD is also beset with difficulties. Most anti osteoporosis agents are currently contraindicated in patients with creatinine clearance less than 30 ml/ min/m2. In addition to the potential for worsening of renal function, the very real worry of worsening possible adynamic bone disease and thereby causing fractures with the use of potent anti resorptives exist. This presentation will aim to address the issues surrounding the diagnosis of osteoporosis in CKD as well as will the difficulties surrounding its treatment and will explore some of the currently available treatment options of this difficult disease.

SE-2-2

Vitamin D: Molecular Actions Across a Variety of Biological Systems

Howard a MorrIs

Department of Chemical Pathology, SA Pathology and School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia 5000 Australia

Reports describing health risks due to inadequate vitamin D status continue to generate considerable interest. Recent research on the various molecular activities of the vitamin D system provides evidence of its capability to exert biological effects across a wide range of tissues similar to other nuclear receptor hormones. These activities include endocrine and paracrine or autocrine actions, vitamin D metabolism in a wide range of tissues and modulation of gene expression by interaction of the nuclear vitamin D receptor with other gene transcription factors.

The endocrine action of 1,25-dihydroxyvitamin D plays critical roles in the maintenance of plasma calcium and phosphate through actions at the intestine to increase calcium absorption, renal tubular reabsorption and bone resorption. 25-hydroxyvitamin D metabolism to 1,25-dihydroxyvitamin D occurs in the kidney to maintain plasma levels as well as in a wide range of tissues where it does not contribute to plasma levels but exerts only local activities. The three major bone cell types, osteoblasts, osteocytes and osteoclasts, can all metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Vitamin D activities in the skeleton include endocrine actions to stimulate bone resorption and inhibit bone formation. Current research indicates that local synthesis of 1,25-dihydroxyvitamin D within osteoblasts together with adequate dietary calcium stimulates bone formation. Thus dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on the bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient.

The nuclear vitamin D receptor exerts its classical action when 1,25-dihydroxyvitamin D binds by dimerising with the retinoid X receptor to bind to DNA sequences known as vitamin D response elements. Such binding results in recruitment of a large number of proteins making up the transcriptional complex to modulate messenger RNA transcription of vitamin D responsive genes. The 1,25-dihydroxyvitamin D-nuclear vitamin D complex can also initiate the cytoplasmic MAP kinase signalling pathway to enhance gene transcription. The nuclear vitamin D receptor can bind to other transcription factors such as β-catenin or Fox0 to regulate β-catenin or Fox0 responsive genes respectively. These transcriptional regulators are important in cell proliferation and this is a particular mechanism by which vitamin D can inhibit cell proliferation.

This knowledge provides physiological plausibility of the various health benefits claimed to be provided by vitamin D and supports the proposals for conducting clinical trials. It also informs the design of such trials. Vitamin D interacts with dietary calcium intake to modulate bone mineral homeostasis. With a low dietary calcium intake For example many systematic reviews and metaanalyses.

SE-2-3

Recent Advances in Osteoporosis Research in Taiwan

Jung-Fu CHen

Division of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

A growing elderly population is expected globally (Silver Aging Tsunami) and osteoporotic fractures now become a major epidemic , and the heavy burden of hip fractures on health care system will continue to exacerbate. Taiwan just caught the 9th worldwide role but 1st in Asia with annual incidence of hip fractures in women and men according to the hip fracture map of IOF (2012).

According to the Nutrition and Health Survey in Taiwan (NAHSIT 2004-2008), the BMD study showed that the prevalence of femoral neck osteoporosis in individuals aged over 50 was 10.7% for men, and 12.1% for women. The prevalence increased to 22.57% and 41.17% respectively. Using Taiwan’s National Health Insurance claim data,we have showed the rising annual incidence of hip fractures did stabilize and decline progressively since 2005; but owing to the size of aging population, the number of hip fractures is expected to inflate yearly from 18,338 in 2010 to 50,421 in 2035—a 2.7fold increase.

Furthermore there are many studies revealing the association with co-morbidity, such as diabetics did have HR 1.66 for fracture, also with higher post fracture deep wound infection, septicemia, and mortality, and the overall HRs for major osteoporotic fracture were 1.24 in men and 1.18 in women with CVD , especially cerebrovascular disease (HR 1.31) and heart failure (HR1.18). We do have seen greater hip fracture risk in Individuals with dementia (HR1.92), sleep disorders (HR 2.74), Parkinson’s disease (HR 2.71), schizophrenia (HR 1.57), dementia (HR 1.92), inflammatory bowel disease (HR 1.31), repeatedly addressing the importance of patient-centered comprehensive care.

Unexceptionally adherence to osteoporotic regimens was still sub-optimal ,the majority of patients’ decreased adherence just within the first year,and although varieties of anti-fracture medicines are reimbursed by govemental insurance, efficacy and some SAE are proved and needed scheduled monitoring. However Taiwan NHI data showed the gap that only 27 % of hip fracture patients received BMD tests and only 34 % received drug treatment. The awareness of osteoporosis management among Taiwan patients and physicians still needs to be improved.