Strontium ranelate
Encyclopedia
Strontium ranelate, a strontium(II)
salt of ranelic acid
, is a medication for osteoporosis
marketed as Protelos or Protos by Servier. It is unusual in the sense that it both increases deposition of new bone osteoblast
s and reduces the resorption of bone by osteoclast
s. It is therefore promoted as a "dual action bone agent" (DABA).
Strontium ranelate stimulates the calcium
sensing receptors and leads to the differentiation of pre-osteoblast to osteoblast
which increases the bone formation. Strontium ranelate also stimulates osteoblasts to secrete osteoprotegerin
in inhibiting osteoclasts formed from pre-osteoclasts in relation to the RANKL
system, which leads to the decrease of bone resorption.
Strontium ranelate is unusual in that the cation (strontium) is responsible for the pharmacological effect, whereas in most modern medications it is the base (anion) that is the active ingredient. In early scientific pharmacology, cations such as arsenic, bismuth, mercury and lithium were frequently used but recently anions have been much more in vogue.
osteoporosis
to reduce the risk of vertebral and hip fractures. In the United States, Strontium Ranelate is not approved by the FDA. In the United Kingdom, Strontium Ranelate is prescribed under the National Health Service
as a medicine for the treatment of post menopausal osteoporosis.
2 major phase III clinical studies, SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis), were started in 2000 to investigate the efficacy of strontium ranelate in reducing vertebral fractures and peripheral fractures, including hip fractures. In the 3 years results, reported in 2004, strontium ranelate showed significant reduction in vertebral fractures with 41% and hip fractures with 36% compared with patients treated with placebo.
The efficacy was sustained in 5 years data. The 5 years data confirmed that strontium ranelate can reduce the vertebral fractures significantly no matter the risk factors of the osteoporotic women have. These include their age (<70, 70-80 and >80), bone mineral density (osteoporotic and osteopenia), prevalent fractures (0 prevalent fracture, 1-2 prevalent fractures and >2 prevalent fractures), symptomatic fractures, body mass index
and smoking.
Strontium ranelate shows antifracture efficacy in very old elderly and osteopenic patients. It is generally well tolerated.
antibiotics, as these chelate
the active substance.
, diarrhea
, headache
and eczema
, but with only 2–4% increase compared with placebo group. However, most of the side effects resolved within 3 months.
Strontium
Strontium is a chemical element with the symbol Sr and the atomic number 38. An alkaline earth metal, strontium is a soft silver-white or yellowish metallic element that is highly reactive chemically. The metal turns yellow when exposed to air. It occurs naturally in the minerals celestine and...
salt of ranelic acid
Ranelic acid
Ranelic acid is an organic acid capable of chelating metal cations.It forms the ranelate ion, C12H6N2O8S4-. Strontium ranelate, made by combining strontium with ranelic acid, is a drug used to treat osteoporosis and increase bone mineral density ....
, is a medication for osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
marketed as Protelos or Protos by Servier. It is unusual in the sense that it both increases deposition of new bone osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
s and reduces the resorption of bone by osteoclast
Osteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
s. It is therefore promoted as a "dual action bone agent" (DABA).
Mode of action
Strontium ranelate is an antiosteoporotic agent which both increases bone formation and reduces bone resorption, resulting in a rebalance of bone turnover in favor of bone formation. This is similar to the effects of choline stabilized orthosilicic acid.Strontium ranelate stimulates the calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
sensing receptors and leads to the differentiation of pre-osteoblast to osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
which increases the bone formation. Strontium ranelate also stimulates osteoblasts to secrete osteoprotegerin
Osteoprotegerin
Osteoprotegerin , also known as osteoclastogenesis inhibitory factor , or tumor necrosis factor receptor superfamily member 11B , is a protein that in humans is encoded by the TNFRSF11B gene...
in inhibiting osteoclasts formed from pre-osteoclasts in relation to the RANKL
RANKL
Receptor activator of nuclear factor kappa-B ligand , also known as tumor necrosis factor ligand superfamily member 11 , TNF-related activation-induced cytokine , osteoprotegerin ligand , and osteoclast differentiation factor , is a protein that in humans is encoded by the TNFSF11 gene.RANKL is...
system, which leads to the decrease of bone resorption.
Strontium ranelate is unusual in that the cation (strontium) is responsible for the pharmacological effect, whereas in most modern medications it is the base (anion) that is the active ingredient. In early scientific pharmacology, cations such as arsenic, bismuth, mercury and lithium were frequently used but recently anions have been much more in vogue.
Indication
Strontium ranelate is registered as a prescription drug in more than 70 countries for the treatment of post-menopausalMenopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
to reduce the risk of vertebral and hip fractures. In the United States, Strontium Ranelate is not approved by the FDA. In the United Kingdom, Strontium Ranelate is prescribed under the National Health Service
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
as a medicine for the treatment of post menopausal osteoporosis.
2 major phase III clinical studies, SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis), were started in 2000 to investigate the efficacy of strontium ranelate in reducing vertebral fractures and peripheral fractures, including hip fractures. In the 3 years results, reported in 2004, strontium ranelate showed significant reduction in vertebral fractures with 41% and hip fractures with 36% compared with patients treated with placebo.
The efficacy was sustained in 5 years data. The 5 years data confirmed that strontium ranelate can reduce the vertebral fractures significantly no matter the risk factors of the osteoporotic women have. These include their age (<70, 70-80 and >80), bone mineral density (osteoporotic and osteopenia), prevalent fractures (0 prevalent fracture, 1-2 prevalent fractures and >2 prevalent fractures), symptomatic fractures, body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
and smoking.
Strontium ranelate shows antifracture efficacy in very old elderly and osteopenic patients. It is generally well tolerated.
Contraindications
Strontium ranelate is contraindicated in hypersensitivity to the active substance or to any of the excipients. It is not recommended in patients with severe renal disease, i.e. creatinine clearance below 30 mL/min due to lack of data. Precaution is advised in patients at increased risk of venous thromboembolism (VTE), including patients with a past history of VTE. Precaution is advised in patients with phenylketonuria, as strontium ranelate contains phenylalanine. Precaution as it interferes with colorimetric measurements of calcium in blood and urine.Interactions
According to the manufacturer, strontium ranelate should be taken 2 hours apart from food, milk and derivative products, and medicinal products containing calcium. Should be taken 2 hours before antacids. Treatment should be suspended while taking oral tetracycline and quinoloneQuinolone
The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....
antibiotics, as these chelate
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
the active substance.
Side effects
The most common side effects include nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
, but with only 2–4% increase compared with placebo group. However, most of the side effects resolved within 3 months.