See also non-immune cells (for discussion of osteoblasts and osteoclasts)
Osteoporosis; Introduction:
Osteoprosis is characterised by a progressive loss of bone mass and microarchitecture which leads to incrased fracture risk. The World Helath Organization (wHO) defines osteoporsis as a systemic skeletal disease characterised by low bone mass and microarhitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. with the ageing of the population, the complications of osteoporsis, fractures, represent a growing medical and socio-economic threat in industrialised countires. Switzerland belogs to the countries with the highest and still fastest growing life expectancy at birth worldwide (84.6 years for women and 80.2 for men in 2010). As the incidence of osteoporotic fractures increases exponentially with age, the implementation of meassures aimed at reducing fracture risk is needed to preserve quality of life and to ensure adqueate control of health care costs. “Kurt Lippuner, “the future of osteoporsis treatment –a research update” Current opinion, July 2012).
Types of Osteoporsis:
The goal of steoporsis treatment is to reduce fractures . this can be acheived either by decreasing bone resorption and/or by increasing bone formation.
Primary Osteoporsis: is linked to the normal aging process. There is a link between two hormones, estrogen and progesteron and teh rate at hwih bone is lost. Estrogen regulates osteoclasts that break down bone and progesterone controls osteoblasts, which help in making new bone. Other hromones are also important. Primary osteoporsis can be divided into “primary type I and “primary type II” osteoporsis.
–Primary Type I osteoporsis: is generally referred to as postmenopausal osteoporsis, as it is seen in women six times more frequently who have gone through menopause, resulting in a drop in levels of estrogen. It occurs in women about 10-15 years after menopause, usually between age 50 and 70. The loss of bone structure because of the increase in bone resorption is connected to estrogen deficiency in women and the lack of testosterone in men. People who suffer from primary type I osteoporosis are at high risk of spinal and wrist factures.
–Primary Type II osteoporosis: is caused by a long term calcium deficiency. Women are twice as more likely than men to suffer form Type II osteoporosis. It results in loss of outer bone structure and also the inner trabecular bone to wear down and become thin. Studies have linked deficiency in dietary calcium and vitam D decline due to age, or the hyper activity of the parathyroid glands (secondary hyperparathyroidism). It is also called low-turnover osteoporsis becasue the rate of bone turnover is much lower in this type of osteoporsis.
Secondary Osteoporisis: develop when certain medical conditions and medications increase bone remodeling leading to disruption of bone reformation. The loss of bone mass occurs due to the imbalance between the production of new bone and the loss of old bone, leading to lower bone turnover rate. An imbalance in hormones from the increased activity of the parathyroid glands or hyperparathyroidism can result in secondary osteoporosis. Hormonal imbalance can also occur form hyperthyroidism, which is an excessive secretion from thyroid glands. Secondary osteoporosis is common among patients sufering form diabetes, which can often lead to hyperglycemia or increasing level of glycosuria. The long term use of oral corticosteroids can cause hypercotisolisms, which increases the chance of developing secondary osteoporsis.
Genes associated with Osteoporosis:
Genome wide association studies (GWASs) have successfully identified hundreds of generic variants assocaited with osteoporosis and related traits, such as bone mineral density (BMD) and fracture. Transcriptone wide association studies have also enhanced the discovery of genetic resk loci for complex traits by integrating gene expression data form large transcriptone reference datasets, such as the Genotype-Tissue Expression product. Alternative ribonucleic acid (RNA) splicing, which removes introns and joins exons in premessenger RNAs (mRNAs) to produce mature mRNAs, can also play important roles in the development of dsiease. For instance, some mutaitons may cause aberrant splicing of specific genes, elading to various skeletal diseases. (Liu, “Gene expression and RNA splicing imputation identifies novel candidate genes assocaited with Osteoporosis” J. Clinical Endocrinology & Metabolism, 202, 105(12),e4742-e4757).
Treatments:
Antibodies against endogenous inhibitors of bone formation scelerostin, dickkkofp-1, PTH and PTHrp analogues.
inhibitors of bone resorption: This includes cathepsin K inhibitors: which may suppress osteoclase function without impairing osteoclast viability and thus maintain bone formation by preserving the osteoclast-osteoblast corsstalk.
–Bisphophonates: are today’s mainstay of osteoporosis treatment. They act as inhibitors of bone resorption with a high affinity for bone and were shwon to increase BMD and reduce fracture risk in patients with postmenopausal, male, and glucocorticosteroid-induced osteoporsis. Due to their long half-life in bone, they can be adminsitered either orally or intravenously.
antibody against RNAKL: such as denosumab which inhibits osteoclast formation, function and survival.