Springer Science and Business Media LLC

Osteoporosis is a common disease with strong genetic control. Genetic linkage and association studies are the two most popular methods used to investigate the genetic basis of osteoporosis. Linkage studies have been successfully used to identify quantitative trait loci (QTLs), and association studies have been widely performed to test candidate genes for osteoporosis. In this article, we review the design and interpretation of linkage and association studies on osteoporosis.

Osteoporosis is characterized by the reduced mass as well as quality of bone, and increased risk of fragility fracture. Skeletal homeostasis is maintained through the balanced activities of osteoclasts and osteoblasts, and osteoporosis is considered to be a metabolic disorder caused by an imbalance between bone resorption and formation. Whereas osteoclasts and osteoblasts have been the primary targets for elucidating the cell-based mechanisms underlying the pathophysiology of osteoporosis, much less attention has been paid to the role of osteocytes. This review focuses on the physiologic function of osteocytes in the regulation of bone and mineral metabolism, summarizing the findings from human disease and mouse genetics, and then extending the discussion to the pathogenetic roles of osteocytes in skeletal aging.

Autocrine, paracrine and endocrine signals regulate the activities of cells involved in skeletal remodelling. Mapping of the metabolic pathways of bone cells and characterization of their chemical mediators have prompted the pharmaceutical industry to develop patented drugs and auto-antibodies which modulate the anabolic and catabolic activities in bone. This overview provides insight into the metabolic pathways which govern bone cells involved in bone metabolism as a framework for understanding the progress made in the pharmaceutical manipulation of skeletal health.

This chapter reviews data on the prevalence of vitamin D deficiency, risk factors that predispose children and adolescents to this problem, and current approaches to routine vitamin D supplementation and treatment of vitamin D deficiency. The increasing world-wide prevalence of vitamin D deficiency among otherwise healthy pediatric patients is explored. Risk factors for vitamin D deficiency have been identified and include, among others, northern geographical location, dark skin pigmentation, female gender, lack of supplementation, and diseases associated with malabsorption. While supplementation strategies to prevent vitamin D deficiency have not been standardized for infants, children, and adolescents, previous studies comparing different doses have been tested in both healthy youth, as well as those with chronic disease. There is even less consensus on the appropriate treatment doses for young patients identified to have this deficiency. Health outcomes data are critically needed to provide guidance regarding the most appropriate supplementation and treatment regimens for the pediatric age group.

Deteriorated bone microarchitecture is a major health concern affecting millions worldwide, amounting to high mortality along with psychological, social, and economic burden. Hypoxia has been known to affect bone mineral metabolism in various in vitro and in vivo experiments in an inconclusive manner and only a few studies are available on natives or travelers of high altitude, pointing towards the deterioration of bone health. HIF proteins, fundamental to hypoxia signaling have also been shown to affect bone remodeling by mediating osteoblastogenesis and osteoclastogenesis but the underlying mechanism of this process is not clear. Most studies have been reported in men but only few in female, while it has been already established that estrogen plays a major role in protecting skeletal health and recent reports identify estrogen as a major player in determining bone quality in men as well. The tough terrain and lack of transport in these areas require optimal bone quality to be maintained for continuous locomotion and load-bearing capacity. The Wnt pathway is involved in load-induced bone formation and sclerostin; the inhibitor of this pathway has been reported to be regulated by both estrogen and HIF proteins. However, the hypobaric hypoxia-operated molecular mechanism regulating the bone quality and microarchitecture in both male and female is still not fully elucidated. Therefore, in this review, available literature on the bone health status under sustained hypoxic exposure focusing on the significance and crosstalk of HIF proteins, Wnt pathway, and estrogen are compiled and discussed to open new aspects of high-altitude bone health research.

The evolution of our understanding of the biological impact of vitamin D is briefly reviewed, with a focus on the physiology and endocrinology of the vitamin D system. This chapter attempts to bring the molecular discoveries in vitamin D metabolism and mechanisms of action into focus on known physiology and endocrinology. The latest developments on metabolism of vitamin D, the enzymes involved, and the genes responsible are presented. The impact of the molecular discoveries on current views of the importance of vitamin D in public health is also presented.

The International Fibrodysplasia Ossificans Progressiva (FOP) Association was, founded by patient Jeannie Peeper in June of 1988 to educate patients, doctors, and the public about FOP: to raise funds and provide a patient base to support medical research into FOP: and to support patients with FOP and their families by providing a network of communication to help end the isolation that accompanies this rare and severely disabling condition.

Dual-energy X-ray absorptiometry (DXA) is a well-established clinical tool for measuring bone mineral density (BMD) in the assessment of patients at risk of fracture. DXA is commonly used to diagnose osteoporosis, assess fracture risk, and assess the skeletal effects of treatment. Non-BMD DXA measurements, such as vertebral fracture assessment, hip access length, and trabecular score, have clinical applications that can guide patient treatment decisions. Quantitative computed tomography (QCT) measures three-dimensional volumetric BMD that is correlated with fracture risk. QCT measurements of the hip can also be used to generate a two-dimensional DXA-equivalent areal BMD and T-score that can be used for diagnosis of osteoporosis and the assessment of fracture risk in the FRAX algorithm. Opportunistic measurements of BMD obtained with CT scans evaluating non-skeletal conditions have potential clinical utility in identifying patients at high risk of fracture. This is a collection of clinical vignettes that illustrate potential applications of non-BMD DXA measurements and CT scanning in the management of patients at risk of fracture.

There is increasing evidence that fracture risk in osteoporosis is not only related to bone mineral density but also to a compilation of factors that are often referred to under the legendary terminology “bone quality”. This article reviews initially the biomechanical aspects of trauma and then the current understanding of the many characteristics of bone that give it strength to resist trauma, including those characteristics that can currently be measured in vivo, those that will shortly be assessable, and those that yet defy measurement in the intact human. The mechanism by which antiresorptive and anabolic therapies for osteoporosis may affect bone strength are also discussed.

Biphosphonate-related osteonecrosis of the jaw (BRONJ) is a devastating side effect of oral bisphosphonates associated with patient morbidity and high financial burden to health services. BRONJ is usually associated with parenteral use of bisphosphonates in oncologic patients, but its incidence among individuals with osteoporosis who take oral bisphosphonates is on the rise. In the absence of definitive treatment for BRONJ, every effort should be made toward its prevention. The patients must be informed about the extremely small but proven risk of oral BRONJ and be recommended to undergo periodic dental evaluation and meticulous oral hygiene. Once BRONJ occurs, long-term antibiotic therapy and superficial curettage may be beneficial.