Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.
Calcium metabolism is the movement and regulation of calcium ions (Ca2+) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).
Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement.
Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes.
Zoledronic acid, also known as zoledronate and sold under the brand name Zometa by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due to cancer, Paget's disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Calcitriol increases blood calcium (Ca2+) mainly by increasing the uptake of calcium from the intestines.
Renal osteodystrophy/adynamic bone disease is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.
X-linked hypophosphatemia (XLH) is an X-linked dominant form of rickets that differs from most cases of dietary deficiency rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short stature and genu varum (bow-leggedness). It is associated with a mutation in the PHEX gene sequence (Xp.22) and subsequent inactivity of the PHEX protein. PHEX mutations lead to an elevated circulating (systemic) level of the hormone FGF23 which results in renal phosphate wasting, and locally in the extracellular matrix of bones and teeth an elevated level of the mineralization/calcification-inhibiting protein osteopontin. An inactivating mutation in the PHEX gene results in an increase in systemic circulating FGF23, and a decrease in the enzymatic activity of the PHEX enzyme which normally removes (degrades) mineralization-inhibiting osteopontin protein; in XLH, the decreased PHEX enzyme activity leads to an accumulation of inhibitory osteopontin locally in bones and teeth to block mineralization which, along with renal phosphate wasting, both cause osteomalacia and odontomalacia. For both XLH and hypophosphatasia, inhibitor-enzyme pair relationships function to regulate mineralization in the extracellular matrix through a double-negative activation effect in a manner described as the Stenciling Principle. Both these underlying mechanisms contribute to the pathophysiology of XLH that leads to soft bones and teeth. The prevalence of the disease is 1 in 20,000.
Calcifediol, also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D3 (abbreviated 25(OH)D3), is a form of vitamin D produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) by the enzyme vitamin D 25-hydroxylase. Calcifediol can be further hydroxylated by the enzyme 25(OH)D-1α-hydroxylase, primarily in the kidney, to form calcitriol (1,25-(OH)2D3), which is the active hormonal form of vitamin D.
25-Hydroxyvitamin D 1-alpha-hydroxylase also known as calcidiol 1-monooxygenase or cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene.
Calcitroic acid (1α-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D3) is a major metabolite of 1α,25-dihydroxyvitamin D3 (calcitriol). Often synthesized in the liver and kidneys, calcitroic acid is generated in the body after vitamin D is first converted into calcitriol, an intermediate in the fortification of bone through the formation and regulation of calcium in the body. During this deactivation process, oxidation reactions at C24 and C23 occur which ultimately lead to side-chain cleavage which helps in the formation of calcitroic acid. These pathways managed by calcitriol are thought to be inactivated through its hydroxylation by the enzyme CYP24A1, also called calcitriol 24-hydroxylase. Specifically, it is thought to be the major route to inactivate vitamin D metabolites.
Cytochrome P450 family 24 subfamily A member 1 (abbreviated CYP24A1) is a member of the cytochrome P450 superfamily of enzymes encoded by the CYP24A1 gene. It is a mitochondrial monooxygenase which catalyzes reactions including 24-hydroxylation of calcitriol (1,25-dihydroxyvitamin D3). It has also been identified as vitamin D3 24-hydroxylase.(EC 1.14.15.16)
An endocrine bone disease is a bone disease associated with a disorder of the endocrine system. An example is osteitis fibrosa cystica.
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol).
The active natural hormonal form of vitamin D is 1,25-dihydroxyvitamin D (1,25(OH)2D). This molecule and other naturally occurring forms of vitamin D, including its precursors and metabolites, have been modified to synthesize pharmaceuticals with potentially greater, or selective, therapeutic actions.
Doxercalciferol (or 1-hydroxyergocalciferol, trade name Hectorol) is drug for secondary hyperparathyroidism and metabolic bone disease. It is a synthetic analog of ergocalciferol (vitamin D2). It suppresses parathyroid synthesis and secretion.
Eldecalcitol is a drug used in Japan for the treatment of osteoporosis. It is an analog of vitamin D. Osteoporosis is a common bone disease among the older generation, with an estimated prevalence of over 200 million people. This condition often results in bone fractures due to abnormally low bone mass density, and is a leading cause of disability, especially among developed countries with longer average life spans. Osteoporosis is more common in women than with men.
Chronic kidney disease–mineral and bone disorder (CKD-MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:
Idiopathic hypercalcinuria (IH) is a condition including an excessive urinary calcium level with a normal blood calcium level resulting from no underlying cause. IH has become the most common cause of hypercalciuria and is the most serious metabolic risk factor for developing nephrolithiasis. IH can predispose individuals to osteopenia or osteoporosis, and affects the entire body. IH arises due to faulty calcium homeostasis, a closely monitored process, where slight deviations in calcium transport in the intestines, blood, and bone can lead to excessive calcium excretion, bone mineral density loss, or kidney stone formation. 50%-60% of nephrolithiasis patients suffer from IH and have 5%-15% lower bone density than those who do not.
