Osteoporosis in chronic diseases is very frequent and pathogenetically varied. It complicates the course of the underlying disease by the occurrence of fractures, which aggravate the quality of life and increase the mortality of patients from the underlying disease. The secondary deterioration of bone quality in chronic diseases, such as diabetes of type 1 and type 2 and/or other endocrine and metabolic disorders, as well as inflammatory diseases, including rheumatoid arthritis - are mostly associated with structural changes to collagen, altered bone turnover, increased cortical porosity and damage to the trabecular and cortical microarchitecture. Mechanisms of development of osteoporosis in some inborn or acquired disorders are discussed.
- MeSH
- Celiac Disease complications genetics metabolism MeSH
- Crohn Disease complications genetics metabolism MeSH
- Diabetes Mellitus genetics metabolism MeSH
- Humans MeSH
- Metabolic Diseases complications genetics metabolism MeSH
- Osteoporosis complications genetics metabolism MeSH
- Bone Remodeling physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The skeleton shows an unconventional role in the physiology and pathophysiology of the human organism, not only as the target tissue for a number of systemic hormones, but also as endocrine tissue modulating some skeletal and extraskeletal systems. From this point of view, the principal cells in the skeleton are osteocytes. These cells primarily work as mechano-sensors and modulate bone remodeling. Mechanically unloaded osteocytes synthetize sclerostin, the strong inhibitor of bone formation and RANKL, the strong activator of bone resorption. Osteocytes also express hormonally active vitamin D (1,25(OH)(2)D) and phosphatonins, such as FGF23. Both 1,25(OH)(2)D and FGF23 have been identified as powerful regulators of the phosphate metabolism, including in chronic kidney disease. Further endocrine cells of the skeleton involved in bone remodeling are osteoblasts. While FGF23 targets the kidney and parathyroid glands to control metabolism of vitamin D and phosphates, osteoblasts express osteocalcin, which through GPRC6A receptors modulates beta cells of the pancreatic islets, muscle, adipose tissue, brain and testes. This article reviews some knowledge concerning the interaction between the bone hormonal network and phosphate or energy homeostasis and/or male reproduction.
- MeSH
- Endocrine System physiology MeSH
- Fibroblast Growth Factor-23 MeSH
- Homeostasis physiology MeSH
- Humans MeSH
- Osteoblasts physiology MeSH
- Osteocytes physiology MeSH
- Bone Remodeling physiology MeSH
- Vitamin D metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- FGF23 protein, human MeSH Browser
- Fibroblast Growth Factor-23 MeSH
- Vitamin D MeSH
In this review the authors outline traditional antiresorptive pharmaceuticals, such as bisphosphonates, monoclonal antibodies against RANKL, SERMs, as well as a drug with an anabolic effect on the skeleton, parathormone. However, there is also a focus on non-traditional strategies used in therapy for osteolytic diseases. The newest antiosteoporotic pharmaceuticals increase osteoblast differentiation via BMP signaling (harmine), or stimulate osteogenic differentiation of mesenchymal stem cells through Wnt/beta-catenin (icarrin, isoflavonoid caviunin, or sulfasalazine). A certain promise in the treatment of osteoporosis is shown by molecules targeting non-coding microRNAs (which are critical for osteoclastogenesis) or those stimulating osteoblast activity via epigenetic mechanisms. Vitamin D metabolites have specific antiosteoporotic potencies, modulating the skeleton not only via mineralization, but markedly also through the direct effects on the bone microstructure.
- MeSH
- Diphosphonates administration & dosage MeSH
- Bone Density drug effects physiology MeSH
- Humans MeSH
- Antibodies, Monoclonal administration & dosage MeSH
- Osteogenesis drug effects physiology MeSH
- Osteoporosis drug therapy metabolism MeSH
- Bone Remodeling drug effects physiology MeSH
- Vitamin D administration & dosage MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Diphosphonates MeSH
- Antibodies, Monoclonal MeSH
- Vitamin D MeSH
Here we analyzed associations between muscles mass, total bone mineral content (BMC), lumbar spine bone density (BMD L1-L4) and serum or urine hormones in healthy peripubertal girls. Total BMC and areal BMD L1-L4, muscle mass and fat were measured by dual-energy X-ray absorptiometry (DXA). Muscle force (N) was estimated by a dynamometer. Circulating estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 25-hydroxy vitamin D, parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), leptin, osteocalcin, bone isoenzyme of alkaline phosphatase (bALP) and total calcium and phosphorus were quantified as the nocturnal melatonin and serotonin urinary excretion. Partial correlations adjusted for height, Tanner score and physical activity confirmed positive relationships between BMC or BMD L1-L4 (Z-score) and lean mass or fat. Furthermore, positive relationship was observed between BMC or BMD L1-L4 (Z-score) and serum leptin. After adjustment for Tanner score and physical activity, positive associations were observed between lean mass and IGF-1, leptin levels or muscle force. We proved positive relationships between bone mass and serum leptin in peripubertal girls.
- MeSH
- Exercise physiology MeSH
- Child MeSH
- Estradiol blood MeSH
- Insulin-Like Growth Factor I metabolism MeSH
- Calcifediol blood MeSH
- Bone Density physiology MeSH
- Leptin blood MeSH
- Humans MeSH
- Adolescent MeSH
- Osteocalcin blood MeSH
- Puberty metabolism MeSH
- Body Composition physiology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Estradiol MeSH
- IGF1 protein, human MeSH Browser
- Insulin-Like Growth Factor I MeSH
- Calcifediol MeSH
- Leptin MeSH
- Osteocalcin MeSH
The protective role of nutrition factors such as calcium, vitamin D and vitamin K for the integrity of the skeleton is well understood. In addition, integrity of the skeleton is positively influenced by certain trace elements (e.g. zinc, copper, manganese, magnesium, iron, selenium, boron and fluoride) and negatively by others (lead, cadmium, cobalt). Deficiency or excess of these elements influence bone mass and bone quality in adulthood as well as in childhood and adolescence. However, some protective elements may become toxic under certain conditions, depending on dosage (serum concentration), duration of treatment and interactions among individual elements. We review the beneficial and toxic effects of key elements on bone homeostasis.
- MeSH
- Homeostasis drug effects physiology MeSH
- Magnesium administration & dosage metabolism MeSH
- Cadmium adverse effects metabolism MeSH
- Bone Density drug effects physiology MeSH
- Humans MeSH
- Lead adverse effects metabolism MeSH
- Trace Elements administration & dosage adverse effects metabolism MeSH
- Iron administration & dosage metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Magnesium MeSH
- Cadmium MeSH
- Lead MeSH
- Trace Elements MeSH
- Iron MeSH
The metabolic pathways that contribute to maintain serum calcium concentration in narrow physiological range include the bone remodeling process, intestinal absorption and renal tubule resorption. Dysbalance in these regulations may lead to hyper- or hypocalcemia. Hypercalcemia is a potentionally life-threatening and relatively common clinical problem, which is mostly associated with hyperparathyroidism and/or malignant diseases (90 %). Scarce causes of hypercalcemia involve renal failure, kidney transplantation, endocrinopathies, granulomatous diseases, and the long-term treatment with some pharmaceuticals (vitamin D, retinoic acid, lithium). Genetic causes of hypercalcemia involve familial hypocalciuric hypercalcemia associated with an inactivation mutation in the calcium sensing receptor gene and/or a mutation in the CYP24A1 gene. Furthermore, hypercalcemia accompanying primary hyperparathyroidism, which develops as part of multiple endocrine neoplasia (MEN1 and MEN2), is also genetically determined. In this review mechanisms of hypercalcemia are discussed. The objective of this article is a review of hypercalcemia obtained from a Medline bibliographic search.
- MeSH
- Hypercalcemia blood genetics physiopathology MeSH
- Hyperparathyroidism blood genetics physiopathology MeSH
- Humans MeSH
- Mutation genetics MeSH
- Calcium blood MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Calcium MeSH
Bone is a target tissue for hormones, such as the sex steroids, parathormon, vitamin D, calcitonin, glucocorticoids, and thyroid hormones. In the last decade, other "non-classic" hormones that modulate the bone tissue have been identified. While incretins (GIP and GLP-1) inhibit bone remodeling, angiotensin acts to promote remodeling. Bone morphogenetic protein (BMP) has also been found to have anabolic effects on the skeleton by activating bone formation during embryonic development, as well as in the postnatal period of life. Bone has also been identified as an endocrine tissue that produces a number of hormones, that bind to and modulate extra-skeletal receptors. Osteocalcin occupies a central position in this context. It can increase insulin secretion, insulin sensitivity and regulate metabolism of fatty acids. Moreover, osteocalcin also influences phosphate metabolism via osteocyte-derived FGF23 (which targets the kidneys and parathyroid glands to control phosphate reabsorption and metabolism of vitamin D). Finally, osteocalcin stimulates testosterone synthesis in Leydig cells and thus may play some role in male fertility. Further studies are necessary to confirm clinically important roles for skeletal tissue in systemic regulations.
- MeSH
- Angiotensins metabolism MeSH
- Models, Biological MeSH
- Endocrine System metabolism MeSH
- Fibroblast Growth Factor-23 MeSH
- Hormones metabolism MeSH
- Incretins metabolism MeSH
- Bone and Bones metabolism MeSH
- Bone Morphogenetic Proteins metabolism MeSH
- Humans MeSH
- Osteocalcin metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Angiotensins MeSH
- FGF23 protein, human MeSH Browser
- Fibroblast Growth Factor-23 MeSH
- Hormones MeSH
- Incretins MeSH
- Bone Morphogenetic Proteins MeSH
- Osteocalcin MeSH
Osteoporosis is a serious disease characterized by high morbidity and mortality due to atraumatic fractures. In the pathogenesis of osteoporosis, except environment and internal factors, such as hormonal imbalance and genetic background, are also in play. In this study candidate genes for osteoporosis were classified according to metabolic or hormonal pathways, which regulate bone mineral density and bone quality (estrogen, RANKL/RANK/OPG axis, mevalonate, the canonical circuit and genes regulating the vitamin D system). COL1A1 and/or COL1A2 genes, which encode formation of the procollagen 1 molecule, were also studied. Mutations in these genes are well-known causes of the inborn disease 'osteogenesis imperfecta'. In addition to this, polymorphisms in COL1A1 and/or COL1A2 have been found to be associated with parameters of bone quality in adult subjects. The authors discuss the perspectives for the practical utilization of pharmacogenetics (identification of single candidate genes using PCR) and pharmacogenomics (using genome wide association studies (GWAS) to choose optimal treatment for osteoporosis). Potential predictors of antiresorptive therapy efficacy include the following well established genes: ER, FDPS, Cyp19A1, VDR, Col1A1, and Col1A2, as well as the gene for the canonical (Wnt) pathway. Unfortunately, the positive outcomes seen in most association studies have not been confirmed by other researchers. The controversial results could be explained by the use of different methodological approaches in individual studies (different sample size, homogeneity of investigated groups, ethnic differences, or linkage disequilibrium between genes). The key pitfall of association studies is the low variability (7-10 %) of bone phenotypes associated with the investigated genes. Nevertheless, the identification of new genes and the verification of their association with bone density and/or quality (using both PCR and GWAS), remain a great challenge in the optimal prevention and treatment of osteoporosis.
- MeSH
- Fractures, Bone epidemiology genetics MeSH
- Bone Density genetics MeSH
- Humans MeSH
- Osteoporosis epidemiology genetics MeSH
- Polymorphism, Genetic genetics MeSH
- Risk Factors MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Bone metabolism is regulated by interaction between two skeletal cells - osteoclasts and osteoblasts. Function of these cells is controlled by a number of humoral factors, including neurohormones, which ensure equilibrium between bone resorption and bone formation. Influence of neurohormones on bone metabolism is often bimodal and depends on the tissue, in which the hormone is expressed. While hypothalamic beta-1 and beta-2-adrenergic systems stimulate bone formation, beta-2 receptors in bone tissue activate osteoclatogenesis and increases bone resorption. Chronic stimulation of peripheral beta-2 receptors is known to quicken bone loss and alter the mechanical quality of the skeleton. This is supported by the observation of a low incidence of hip fractures in patients treated with betablockers. A bimodal osteo-tropic effect has also been observed with serotonin. While serotonin synthetized in brain has osteo-anabolic effects, serotonin released from the duodenum inhibits osteoblast activity and decreases bone formation. On the other hand, both cannabinoid systems (CB1 receptors in the brain and CB2 in bone tissue) are unambiguously osteo-protective, especially with regard to the aging skeleton. Positive (protective) effects on bone have also been shown by some hypophyseal hormones, such as thyrotropin (which inhibits bone resorption) and adrenocorticotropic hormone and oxytocin, both of which stimulate bone formation. Low oxytocin levels have been shown to potentiate bone loss induced by hypoestrinism in postmenopausal women, as well as in girls with mental anorexia. In addition to reviewing neurohormones with anabolic effects, this article also reviews neurohormones with unambiguously catabolic effects on the skeleton, such as neuropeptide Y and neuromedin U. An important aim of research in this field is the synthesis of new molecules that can stimulate osteo-anabolic or inhibiting osteo-catabolic processes.
- MeSH
- Bone and Bones metabolism physiology MeSH
- Humans MeSH
- Neurotransmitter Agents physiology MeSH
- Osteogenesis physiology MeSH
- Bone Remodeling physiology MeSH
- Bone Development physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Neurotransmitter Agents MeSH
Regional migrating osteoporosis (RMO) was observed in young man with episodes of bone pain in bearing joints, which migrated from hip to leg and subsequently to knee on the unilateral side. Dynamic scintigraphy (SPECT) carried out during relapse of pain demonstrated increased accumulation of radioizotope in Lisfrank joint, distal epiphysis of femur and proximal epiphysis of tibia on the unilateral side due to hyperperfusion and high metabolic turnover in these regions of the skeleton. Dia-gnosis of RMO was confirmed by magnetic resonance (MRI), which showed bone marrow edema of corresponding regions. Although RMO is relatively benign disease with spontaneous remissions, infection etiology or the more serious avascular necrosis should be taken into account.
- MeSH
- Adult MeSH
- Femur * pathology MeSH
- Tomography, Emission-Computed, Single-Photon * MeSH
- Knee Joint * pathology MeSH
- Hip Joint * pathology MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Osteoporosis diagnosis MeSH
- Tomography, X-Ray Computed MeSH
- Disease Progression MeSH
- Tarsal Joints pathology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
