How Do I Use Strontium for Osteoporosis?

Anti-osteoporosis drugs are clinically used to treat osteoporosis. According to the occurrence of the disease, there are mainly basic supplements, drugs that inhibit bone resorption and drugs that promote bone formation. In China, osteoporosis has jumped to the seventh place with frequent and frequent diseases, and the incidence rate has increased year by year. There are already 88 million osteoporosis patients, with a total prevalence of 12.4%. The rate is above 50%, and the incidence of fractures is close to one third.

Antiosteoporosis

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Anti-osteoporosis drugs are clinically used to treat osteoporosis. According to the occurrence of the disease, there are mainly basic supplements, drugs that inhibit bone resorption and drugs that promote bone formation. In China, osteoporosis has jumped to the seventh place with frequent and frequent diseases, and the incidence rate has increased year by year. There are already 88 million osteoporosis patients, with a total prevalence of 12.4%. The rate is above 50%, and the incidence of fractures is close to one third.

Osteoporosis (OPeoporosis, OP) is a systemic metabolic disease caused by multiple causes alone or in combination. It is characterized by reduced bone mass, degeneration of bone tissue microstructure, and decreased mechanical properties of bone, accompanied by bone fragility and fractures. Increased risk [1]. Osteoporosis is mainly manifested in the reduction of Bone Mineral Density (BMD) and bone mass, which mainly include the reduction of bone microstructure, bone conversion, bone mineralization, and accumulation of bone micro-injury, which induces a decrease in bone strength and causes Increased fracture risk. According to statistics, at least 44 million elderly people over the age of 50 in the United States are at risk of osteoporosis, of which 10 million are already suffering from osteoporosis, 34 million have low bone density and are at risk of osteoporotic fractures [2]. In China, osteoporosis has jumped to the seventh place with frequent and frequent diseases, and the incidence rate has increased year by year. There are already 88 million osteoporosis patients, with a total prevalence of 12.4%. The rate is more than 50%, and the incidence of fractures is close to one third [3]. Anti-osteoporosis drugs are mainly divided into basic supplements, drugs that inhibit bone resorption, and drugs that promote bone formation.

Anti-osteoporosis drugs are based on the basic conditions of the disease, including basic supplements, drugs that inhibit bone resorption, and drugs that promote bone formation. The basic drugs for drug treatment are calcium and vitamin D. Clinically, inhibition of osteoclast bone resorption is the main treatment measure. The drugs are mainly bisphosphonates, estrogen and its receptor modulators, and calcitonin. Parathyroid hormone is a drug that promotes bone formation. Strontium salts and vitamin K ₂ have anti-bone resorption and promote bone formation.

Prevention and treatment strategies for osteoporosis include basic measures and medications. Among the basic measures, including strengthening diet, focusing on exercise, avoiding bad living habits, preventing falls, etc., the other important thing is to take basic supplements, that is, calcium and vitamin D.

Calcium is the basic supplement to maintain bone metabolism balance and ensure bone health. For postmenopausal and senile osteoporosis patients, proper calcium supplementation can effectively reduce bone loss and improve bone mineralization. Calcium alone can effectively reduce the risk of fractures in menopausal women, and combined with vitamin D is more effective. At the same time, research proves that calcium alone or combined with vitamin D can effectively inhibit bone loss, not only for menopausal osteoporosis, but also for senile osteoporosis. The recommended daily intake of calcium by the Chinese Nutrition Society is 800 mg for adults and 1000 mg for postmenopausal women and the elderly. The average daily calcium obtained by the elderly in our country is about 400 mg. Elemental calcium is 500-600 mg [4]. Vitamin D is also a commonly used additive to protect bone health. Vitamin D supplementation can significantly reduce fractures when vitamin D deficiency occurs, but when vitamin D is sufficient, the effect of vitamin D supplementation is poor, which mainly depends on the level of 25-hydroxyvitamin D in the body. Active vitamin D and its analogs including calcitriol and -calciferol have active effects without liver and kidney hydroxylation. As active vitamin D, it is more suitable for the elderly, liver and kidney dysfunction, and vitamin D metabolism disorders For patients, the common clinical drug is calcitriol (such as Luo Gaiquan, Gai Sanchun, etc.). When supplementing vitamin D, pay attention to the dosage range. When 25-hydroxyvitamin D> 150 g / L, vitamin D poisoning may occur, causing hypercalcemia, constipation, headache, vomiting and other symptoms. In severe cases, arrhythmia, Renal failure, etc. [5].

The main mechanism of the effect of anti-osteoporosis drugs that inhibit bone resorption is: reduce the production of osteoclasts (estrogen) and reduce the activity of osteoclasts (bisphosphonates), promote the apoptosis of osteoclasts, and further Inhibit bone resorption and bone reconstruction space. It slows bone resorption and maintains bone mass. It cannot effectively stimulate bone formation and increase bone mass.

3.1 Hormone replacement therapy and estrogen receptor modulators

Estrogen replacement treatment (ERT) has been considered as a classic drug for the prevention and treatment of menopausal osteoporosis [6-7]. The main mechanism of action of this class of drugs is that estrogen prevents the activation of growth factors and interleukins (mainly IL-6). IL-6 is a highly effective stimulator of bone resorption. Estrogen inhibits the synthesis of IL-6 by osteoclasts and blocks the IL-6 receptor. Estrogen can also increase osteoclast apoptosis. Third, estrogen delays the bone resorption of parathyroid hormone PTH. Therefore, estrogen can effectively inhibit bone resorption, reduce bone turnover, and increase bone density in osteoporosis, especially in menopause. Supplementation of estrogen inhibits bone hyperconversion, reduces the rate of bone remodeling activation, and estrogen can regulate the balance of bone resorption and bone formation in each reconstruction cycle, enabling bone mass to be reduced in a short time after administration due to inhibition of osteoclasts Activation increases bone mass and significantly reduces bone loss [6]. However, the toxic side effects of these drugs have limited their long-term use as first-line anti-osteoporotic drugs. In addition to acting on bones, estrogen also strongly stimulates other tissues, such as breasts and uterus, causing breast cancer and uterine bleeding. Women who have been treated with estrogen alone for more than 5 years have a 20% increase in the incidence of breast cancer. In addition, nausea and loss of appetite are common after taking the drug, which can also cause endometrial hyperplasia and uterine bleeding [8]. The adverse reactions of raloxifene are mainly a slight increase in venous thrombosis. It is contraindicated in patients with a history of venous thromboembolism, a tendency to thrombosis, and long-term bed rest. A small number of patients will have hot flashes and lower limb spasms during medication, and the drug is suspended when the symptoms are severe. Therefore, in the United States and other countries, its side effects have limited the long-term use of estrogen for osteoporosis.

3.2 Bisphosphonates

Bisphosphonate anti-osteoporosis drugs have been widely used clinically. Its effects include inhibiting osteoclast activity, promoting osteoclast apoptosis, thereby inhibiting bone resorption, reducing bone turnover, maintaining positive bone balance, and effectively reducing the incidence of lumbar and hip fractures. Actonel was approved by the US FDA in April 2000 for the prevention and treatment of postmenopausal osteoporosis. Bisphosphonates are actually a class of bone turnover inhibitors that inhibit both osteoblasts and osteoclasts. They exert anti-bone resorption and inhibit bone formation and calcification. There are currently four generations of this class of drugs. The first-generation product is isethionate (Etidronate, also known as Bundling), which has poor anti-bone resorption specificity. The second-generation products clodronate (bone phosphine), pamidronate, and tiludronate all have high specificity for anti-bone resorption, and side effects are also significantly reduced. Substitute products include Alendronate, Fosamax, also known as Gubang, and Risedronate. The fourth generation of bisphosphonates are Ibandronate (Boniva), Zoledronic acid (Reclast). Bisphosphonate side effects include toxic side effects of the kidney, blood, and liver, gastrointestinal side effects, and immunosuppression [6].

The drugs that promote bone formation are mainly parathyroid hormone, prostaglandin E2, statins, lipid-lowering drugs and fluoride. The main mechanism of action of these drugs is to induce bone lining cells or osteoblast precursor cells to become osteoblasts. Increase the number of osteoblasts, promote the differentiation and calcification of osteoblasts, increase the activity of osteoblasts, and inhibit the apoptosis of osteoblasts, thereby promoting bone formation and increasing bone mass.

Parathyroid hormone (PTH) is the first type of osteosynthetic drug approved by the FDA in December 2002 for stimulating bone formation (Teriparatide, Forteo, 20 mcg d). The main mechanism of action of these drugs is to promote bone synthesis, improve bone structure, reduce bone resorption voids, increase bone density and bone strength, increase bone mass, and reduce the risk of fractures in patients with osteoporosis [8]. Clinical studies have proven that daily subcutaneous injection of PTH can effectively reduce vertebral and non-vertebral fractures. However, its continuous application will weaken bone formation, and bone density will gradually decrease after discontinuation [9]. When parathyroid hormone is used in the clinical treatment of osteoporosis, its efficacy will be affected by other anti-osteoporosis drugs. For example, the effect of combination with bisphosphonate is worse than that of PTH alone. Due to its high cost, the drug is generally used in patients with severe osteoporosis or intolerance to other anti-osteoporotic drugs.

Prostaglandin E2 is a strong bone-forming drug that promotes bone synthesis by stimulating osteoblast differentiation and proliferation. However, due to its many systemic effects and low selectivity, it has not been promoted clinically. Such as dinoprostone (dinoprostone) can stimulate bone formation and reduce bone resorption, but there are few reports of clinical applications. Similarly, statin lipid-lowering drugs are still in the basic and clinical research stages.

Fluoride also has the effect of promoting bone formation, but long-term use of fluoride can lead to poor connection of newborn trabecular bone, thereby increasing cortical bone voids and causing increased non-vertebral fractures. The effect of fluoride on increasing cancellous bone mass and reducing fracture incidence can be offset by its increase in cortical bone voids. Therefore, fluoride is now rarely used [6].

Strontium salts are the main group of drugs with both anti-bone resorption and bone formation. Strontium ranelate is a new generation of anti-osteoporosis drug that can act on osteoblasts and osteoclasts at the same time. It has the dual effects of inhibiting bone resorption and promoting bone formation. It can significantly increase bone density and reduce menopause. The risk of vertebrae (40% to 50%) and non-vertebral fractures (16%) in patients with posterior osteoporosis. Strontium can be used as an alternative to bisphosphonates for postmenopausal osteoporosis [10]. Strontium salt, as a unique anti-osteoporosis drug, can reduce the incidence of vertebral and non-vertebral fractures in postmenopausal women and is well tolerated. It represents an important development in the treatment of osteoporosis. Unlike other anti-osteoporotic drugs, strontium salts reduce bone resorption during bone reconstruction and increase bone synthesis, which promotes an increase in bone mass and strength [11].

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[2] Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement, 2000, 17: 1-36.

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[4] Chinese Medical Association Osteoporosis and Bone Mineral Salt Disease Branch. Guidelines for Diagnosis and Treatment of Primary Osteoporosis (2011). Chinese Journal of Osteoporosis and Bone Mineral Salt Disease, 2011, 4 (1): 2- 17.

[5] Feng Yingyu, Xiuling Ling, Su Lei. Drug treatment of osteoporosis. Medical Review, 2014, 20: 105-109.

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[8] Papapoulos S, Makras P. Selection of antiresorptive or anabolic treatments for postmenopausal osteoporosis. Nat Clin Pract Endocrinol Metab, 2008, 4 (9): 514-523.

[9] Committee to review dietary reference intakes for vitamin D andcalcium. Dietary Reference Intakes for calcium and vitamin D [M]. Washington DC: Institute of Medicine, 2010.

[10] Poole KE, Compston JE. Osteoporosis and its management. BMJ, 2006, 333 (7581): 1251-1256.

[11] Zhang Zhaochuan, Lu Junxian, Xiong Chuanzhi. The role of strontium salt in the treatment of osteoporosis. Modern