Osteoporosis is a multifactorial progressive

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1 Osteoporosis: Current Management Guidelines Harmanjit Singh*, Manoj Goyal**, Jasbir Singh Abstract Osteoporosis is a multifactorial progressive skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture. Fragility fractures, the consequence of osteoporosis, are responsible for excess mortality, morbidity, chronic pain, admission to hospitals and economic costs. Approximately 1.6 million hip fractures occur each year worldwide and the incidence is set to increase to 6.3 million by Preventive measures should be started at an early age and should include smoking cessation and weight-bearing exercises. Pharmacologic prevention methods include calcium supplementation and administration of raloxifene or bisphosphonates. No treatment can completely reverse established osteoporosis. Early intervention can prevent osteoporosis in most people. For patients with established osteoporosis, medical intervention can halt its progression. Currently available therapies include bisphosphonates, selective estrogen receptor modulators (SERMs), hormone replacement therapy (HRT), denosumab, teriparatide, calcitonin and strontium ranelate. Cathepsin K inhibitors (balicatib and odanacatib) are among recent drugs under development. Saracatinib, a novel orally available competitive inhibitor of Src kinase has been shown to inhibit bone resorption in vitro. Lasofoxifene, bazedoxifene and arzoxifene are new SERMs in late-stage treatment trials. Nonpharmacological measures are required when patients experience adverse effects because of drug therapy, when symptoms are not controlled by drug therapy alone or when patient is not willing to take drugs for a prolonged duration. Keywords: Fragility fractures, bisphosphonates, SERMs, Src kinase Osteoporosis is a multifactorial progressive skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, predisposing it to increased fracture risk. Osteoporosis is called a silent disease because it progresses without symptoms and remains unnoticed for a long time as bone resorption process in early stages is almost asymptomatic and at later stages usually presents with a fracture due to trivial trauma. 1 Fragility fractures, the consequence of osteoporosis, are responsible for excess mortality, morbidity, chronic pain, admission to institutions and economic costs. They represent 80% of all fractures in menopausal women over age 50. Patients with hip or vertebral fractures have substantially increased risk of death after the fracture. With major improvements in diagnostic technology and assessment facilities; it is now possible to detect the disease before fractures occur. Once the condition *Senior Resident Dept. of Pharmacology, PGIMER, Chandigarh **Associate Professor Dept. of Pharmacology, MMIMSR, Mullana, Haryana Lecturer Dept. of Pharmacology, GMC, Patiala Address for correspondence Dr Harmanjit Singh Dept. of Pharmacology, PGIMER, Chandigarh harman_gmcp@yahoo.com is diagnosed, steps can be taken to prevent further damage, including special exercises, changes in the diet, lifestyle changes and supplements or medication. Burden of Osteoporosis According to various surveys, worldwide one in 3 women over 50 will suffer a fracture due to osteoporosis; this increases to one in 2 in women over 60. One in 5 men over 50 will suffer a fracture due to osteoporosis; this increases to one in 3 over 60. Approximately 1.6 million hip fractures occur each year worldwide and the incidence is set to increase to 6.3 million by Currently and there is an increasing incidence of hip fractures in the developed cities in Asia. One out of 4 hip fractures occur in Asia and Latin America. 3 Osteoporosis is also becoming a serious public health problem in India. Conservative estimates in a study suggest that 20% of women and about 10-15% of men are osteoporotic in India. 4 Another highly conservative estimate by a group of experts suggested that 26 million Indians suffer from osteoporosis, and this number is expected to reach 36 million by WHO definition of Osteoporosis 6 The World Health Organization (WHO) operationally defines osteoporosis as a bone density that falls Indian Journal of Clinical Practice, Vol. 23, No. 12, May 2013

2 standard deviations (SD) below the mean for young healthy adults of the same sex - also referred to as a T-score of 2.5. Postmenopausal women who fall at the lower end of the young normal range (a T-score 1.0) are defined as having low bone density and are also at increased risk of osteoporosis. More than 50% of fractures among postmenopausal women, including hip fractures, occur in this group with low bone density. The WHO definition applies to postmenopausal women and men aged 50 years or older. This diagnostic classification should not be applied to premenopausal women, men younger than 50 years or children. Bone mineral density (BMD) in a patient is related to peak bone mass and subsequently, bone loss. The T-score is the patient s bone density compared with the BMD of control subjects who are at their peak BMD, while the Z-score reflects a bone density compared with that of patients matched for age and sex. Several noninvasive techniques are available for estimating skeletal mass or density. They include dualenergy X-ray absorptiometry (DXA), single-energy X-ray absorptiometry (SXA), quantitative computed tomography (CT) and ultrasound (US). DXA is a highly accurate X-ray technique that has become the standard for measuring bone density in most centers. 7 Pathophysiology Osteoporosis is classified as primary and secondary. Primary osteoporosis by convention is of relatively unknown origin that occurs with aging and accelerates with menopause or andropause. There is no direct or singular cause for primary osteoporosis but there are several clinical risk factors (Table 1). Secondary osteoporosis is the consequence of conditions such as hormonal imbalances, diseases or medications. It is increasingly being recognized that multiple pathogenetic mechanisms operate in the development of the osteoporotic state. The hallmark of osteoporosis is a reduction in skeletal mass caused by an imbalance between bone resorption and bone formation. Under physiologic conditions, bone formation and resorption are in a fair balance. A change in either that is, increased bone resorption or decreased bone formation may result in osteoporosis. Osteoclasts derived from mesenchymal cells are responsible for bone resorption, whereas osteoblasts from hematopoietic precursors are responsible for bone formation. These two types of cells are dependent on each other for production and linked in the process of bone remodeling. Osteoblasts not only secrete and mineralize osteoid but also appear to control the bone resorption carried out by osteoclasts. Osteocytes, which are terminally differentiated osteoblasts embedded in mineralized bone, direct the timing and location of bone remodeling. In osteoporosis, the coupling mechanism between osteoclasts and osteoblasts is thought to be unable to keep up with the constant microtrauma to trabecular bone. Osteoclasts require weeks to resorb the bone, whereas osteoblasts need months to produce new bone. Osteoclasts resorbs the bone matrix by secreting hydrochloric acid, which dissolves calcium phosphate, and enzymes such as collagenase and other proteases. Therefore, any process that increases the rate of bone remodeling results in net bone loss over time. Furthermore, in periods of rapid remodeling (e.g., after menopause), bone is at an increased risk for fracture because the newly produced bone is less densely mineralized, the resorption sites are temporarily unfilled and the isomerization and maturation of collagen are impaired. The receptor activator of nuclear factor-k B ligand (RANKL)/receptor activator of nuclear factor-k B (RANK)/osteoprotegerin (OPG) system is the final common pathway for bone resorption. Osteoblasts and activated T cells in the bone marrow produce the RANKL cytokine. RANKL binds to RANK expressed by osteoclasts and osteoclast precursors to promote osteoclast differentiation. Osteoprotegerin is a soluble decoy receptor that inhibits RANK-RANKL by binding and sequestering RANKL. 8,9 Risk factors Risk factors for osteoporosis, such as advanced age and reduced BMD, have been established by virtue of their direct and strong relationship to the incidence of fractures; however, many other factors have been considered risk factors based on their relationship to BMD as a surrogate indicator of osteoporosis (Table 1). Management The most important measure in the management of osteoporosis is treatment of the underlying cause. Various preventive treatment measures have been described below. Measures to Prevent Osteoporosis Primary prevention of osteoporosis starts in childhood. Patients require adequate calcium intake, vitamin D intake and weight-bearing exercise. Beyond this, prevention of osteoporosis has two components: Indian Journal of Clinical Practice, Vol. 23, No. 12, May

3 Table 1. Risk Factors for Osteoporosis and Drugs causing Osteoporosis Nonmodifiable Potentially modifiable yadvanced age ( 50 years) y Female sex ywhite or Asian ethnicity ygenetic factors as family history of osteoporosis y Dementia ycigarette smoking y Low body weight (<58 kg or 127 lb) yrecurrent falls yinadequate physical activity y Estrogen deficiency y Drugs* yalcohol use yearly menopause yprolonged premenopausal amenorrhea yandrogen or estrogen deficiency y Calcium deficiency ypoor health *Drugs: Anticonvulsants (phenytoin, carbamazepine, phenobarbitone, valproate), heparin, lithium, chemotherapeutic agents, cyclosporine, systemic steroids, thyroxine supplements, GnRH agonist, aromatase inhibitors. Behavior modification and pharmacologic interventions. The following behaviors should be modified to reduce the risk of developing osteoporosis: Cigarette smoking, physical inactivity and intake of alcohol, sodium, animal protein. Patients should be counseled on smoking cessation and moderated alcohol intake. Patients who have medical disorders and are on medications* (Table 1) that can cause or accelerate bone loss should receive calcium and vitamin D supplementation and in some cases, pharmacologic treatment. Exercise Exercises are another way to maintain BMD, prevent the progression of osteoporosis and reduce the risk of developing bone fractures. A combination of weightbearing and strength training exercises are most effective. Even just walking or jogging regularly can help prevent osteoporosis. A walking program is the best way to start; activities like dancing, aerobics, racquet sports, running and the use of gym equipment are also recommended, depending upon the patient s preference and general condition. Exercise has beneficial effect on neuromuscular function, and improves coordination, balance and strength, thereby reducing the risk of falling. Weight-bearing exercises should be started at early age. Exercise habits should be consistent, at least three times a week as more substantial effect on bone mass is likely if exercise is continued over a long period of time. The beneficial effect wanes if exercise is discontinued Pharmacologic prevention Pharmacologic prevention methods include calcium supplementation and administration of raloxifene or bisphosphonates (alendronate or risedronate). Bisphosphonates and raloxifene should be considered as first-line agents for the prevention of osteoporosis. Calcium supplementation: The goal of the current recommendations for daily calcium intake is to ensure that individuals maintain an adequate calcium balance. Current recommendations from the American Association of Clinical Endocrinologists (AACE) for daily calcium intake are as follows. 15 Age 0-6 months: 200 mg/day Age 6-12 months: 260 mg/day Age 1-3 years: 700 mg/day Age 4-8 years: 1,000 mg/day Age 9-18 years: 1,300 mg/day Age years: 1,000 mg/day Age 50 years: 1,200 mg/day Pregnant and breastfeeding women 18 years: 1,300 mg/day Pregnant and breastfeeding women 19 years: 1,000 mg/day Vitamin D supplementation: Vitamin D is increasingly being recognized as a key element in overall bone health and muscle function. It plays a significant role in bone health, calcium absorption, balance (e.g., reduction in risk of falls) and muscle performance. The minimum daily requirement in patients with osteoporosis is 800 IU of vitamin D 3, or cholecalciferol. Many patients require higher levels (continuously or for a short period) to be considered vitamin D replete, which is defined as a serum 25-hydroxyvitamin D level of 32 ng/ml. Vitamin D is available as ergocalciferol (vitamin D 2 ) 844 Indian Journal of Clinical Practice, Vol. 23, No. 12, May 2013

4 and cholecalciferol (vitamin D 3 ). Vitamin D is metabolized to active metabolites. These metabolites promote the active absorption of calcium and phosphorus by the small intestine, elevating serum calcium and phosphate levels sufficiently to permit bone mineralization Other nutrients 10,11,19 Adequate dietary intake of salt, animal protein. Adequate vitamin K status (required for optimal carboxylation of osteocalcin). Dietary phytoestrogens derived from soya products and legumes (exert estrogenic activity). Pharmacotherapy of Osteoporosis Currently, no treatment can completely reverse established osteoporosis. Early intervention can prevent osteoporosis in most people. For patients with established osteoporosis, medical intervention can halt its progression. If secondary osteoporosis is present, treatment for the primary disorder should be provided. Therapy should be individualized based on each patient s clinical scenario, with the risks and benefits of treatment discussed between the clinician and patient. The National Osteoporosis Foundation (NOF, 2010) 20 recommends that pharmacologic therapy should be reserved for postmenopausal women and men aged 50 years or older who present with the following: A hip or vertebral fracture (vertebral fractures may be clinical or morphometric i.e., identified on a radiograph alone) T-score of 2.5 or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes Low bone mass (T-score between 1.0 and 2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture of 3% or greater or a 10-year probability of a major osteoporosis-related fracture of 20% or greater based on the US-adapted WHO algorithm. Guidelines from the AACE, 15 published in 2010, include the following recommendations for choosing drugs to treat osteoporosis: First-line agents: Alendronate, risedronate, zoledronic acid, denosumab Second-line agent: Ibandronate Second- or third-line agent: Raloxifene (SERMs) Last-line agent: Calcitonin Treatment for patients with very high fracture risk or in whom bisphosphonate therapy has failed: Teriparatide. Bisphosphonates The most commonly prescribed drugs to treat osteoporosis are bisphosphonates. Alendronate was the first bisphosphonate to be approved for treatment of osteoporosis in the US in Since that time, newer bisphosphonates with less frequent dosing intervals have been introduced, partially in an attempt to improve compliance. Risedronate is an oral medication that can be administered daily, weekly or monthly at varying doses. Zoledronic acid is the newer medication, which is administered once yearly by intravenous (IV) transfusion. Bisphosphonates bind to hydroxyapatite crystals and thus have a very high affinity for bone. Bisphosphonates are released from the bone matrix upon exposure to acid and enzymes secreted by an active osteoclast. Out of all bisphosphonates, zoledronic acid has the highest affinity for binding to the bone mineral matrix followed by pamidronate > alendronate > ibandronate > risedronate > etidronate > clodronate. Bisphosphonates with higher affinity like zoledronic acid bind avidly to the bone surface, but spread through bone slowly, whereas lower affinity agents like clodronate distribute more widely through the bone, but they have shorter time of residence when the treatment is stopped. Suppression of bone resorption occurs within approximately three months of initiation of oral bisphosphonate therapy regardless of dosing frequency, but it is more rapid after IV administration. After three years of treatment, bisphosphonates have been shown to increase BMD of the hip by 3-6% and at the spine by 5-8%. In women with osteoporosis, zoledronic acid, alendronate and risedronate also reduced nonvertebral fractures by 25-40%, including hip fractures by 40-60%. 21,22 Dose: Zoledronic acid: 5 mg single IV infusion annually, alendronate: 10 mg/day orally, ibandronate: 2.5 mg oral daily or 150 mg once monthly, risedronate: 5 mg/day oral. Some important adverse events associated with bisphosphonates therapy: Orally administered bisphosphonates may cause irritation in the esophagus. It is recommended to swallow oral bisphosphonates with full glass of plain water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and discontinuing the drug promptly if esophageal symptoms develop. Rapid IV administration of parenteral bisphosphonates may cause renal toxicity. For patients with creatinine clearance Indian Journal of Clinical Practice, Vol. 23, No. 12, May

5 <30-35 ml/min, use of parenteral bisphosphonates is not recommended. Other concerns are risk of kidney damage, osteonecrosis of jaw (Zoledronic acid), atypical fractures and atrial fibrillation Selective estrogen receptor modulators Selective estrogen receptor modulators (SERMs) are nonsteroidal molecules that bind with high affinity to the estrogen receptor (ER) and act as agonists or antagonists depending on the target tissue. The ER agonist effects of SERMs in bone have proven to be important for the treatment of osteoporosis in postmenopausal women. Currently, raloxifene is the only SERM approved by the US Food and Drug Administration (FDA) for prevention and treatment of postmenopausal osteoporosis. Clinical studies have clearly demonstrated the efficacy of raloxifene in significantly reducing the risk of vertebral fracture. Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women. The usual dose is 60 mg given orally daily. It can also be given in combination with calcium and vitamin D. Raloxifene is the first SERM studied for breast cancer prevention, and it decreases bone resorption through actions on ER. It has been shown to prevent bone loss, and data in females with osteoporosis have demonstrated that raloxifene causes a 35% reduction in the risk of vertebral fractures. It has also been shown to reduce the prevalence of invasive breast cancer. Prospective clinical trial data have not shown efficacy at nonvertebral and hip sites. An additional benefit and indication is prevention of ER-positive breast cancer The limited antifracture efficacy of raloxifene has led to interest in developing other SERMs that might have a broader antifracture profile. Lasofoxifene, bazedoxifene and arzoxifene are new SERMs in late-stage treatment trials. RANK-Ligand inhibition: Denosumab Denosumab is a fully human monoclonal antibody that binds with high affinity and specificity to the RANKL, a key mediator of osteoclast formation, activity and survival. The inhibition of RANKL by denosumab reduces osteoclast-mediated bone resorption. It is indicated for the treatment of postmenopausal women with osteoporosis who are at high-risk of fracture (defined as a history of osteoporotic fracture), have multiple risk factors for fracture, are intolerant to other available osteoporosis therapies or in whom osteoporosis therapies have failed. In postmenopausal women with osteoporosis, denosumab reduces the incidence of vertebral, nonvertebral and hip fractures. Denosumab was approved by the US FDA in June Approved dosage is 60 mg given subcutaneously every six months. Several recent studies have demonstrated the efficacy of this new antiresorptive therapeutic class in terms of increasing BMD, decreasing bone turnover markers (BTMs) and most important, reducing fractures at vertebral, hip and other nonvertebral sites. Because RANKL is expressed in lymphocytes, safety concerns relate to inhibition of this important immunomodulator and to potential consequences such as infections. The clinical trials did not report an increased rate of serious infections related to denosumab, but there was a significantly increased incidence of eczema and hospitalization for cellulitis compared with placebo. 31,32 Calcitonin Calcitonin is a hormone that decreases osteoclast activity, thereby impeding postmenopausal bone loss. It acts like the endogenous form of the hormone on the calcitonin receptor on osteoclasts to decrease their activity. Out of all recombinant or synthetic calcitonins that have been used for medical purposes, the salmon calcitonin preparation (SCT) is the most widely used. SCT as a nasal spray is the most commonly used calcitonin formulation due to its convenience of administration. It is recommended in conjunction with adequate calcium and vitamin D intake to prevent the progressive loss of bone mass. The intranasal spray is delivered as a single daily spray that provides 200 IU of the drug. The drug can be delivered subcutaneously, but this route is rarely used. It has reduced the incidence of vertebral fractures in women with pre-existing vertebral fractures. As a desirable additional effect, calcitonin has been noted to reduce the pain of clinical vertebral fractures. Calcitonin is an option for patients who are not candidates for other available osteoporosis treatments. Common side effects of nasally administered calcitonin include nasal discomfort, rhinitis, irritation of nasal mucosa and occasional epistaxis. Nausea, local inflammatory reactions at the injection site, sweating and flushing are side effects noted with parenteral use Strontium ranelate Strontium ranelate, a novel orally active agent, has been developed for the treatment of osteoporosis. It consists of two atoms of strontium and an organic moiety ranelic acid. Strontium ranelate acts by both stimulating bone formation and decreasing bone resorption. In vitro, strontium ranelate has been shown to increase osteoblastic activity, including increasing 846 Indian Journal of Clinical Practice, Vol. 23, No. 12, May 2013

6 collagen synthesis and modulating the OPG/RANKL system in favor of OPG, as well as decrease bone resorption by decreasing osteoclast differentiation and resorbing activity and increasing osteoclast apoptosis. Strontium ranelate is approved for the treatment of osteoporosis in some countries in Europe. It reduces the risk of both spine and nonvertebral fractures. Strontium is not approved for the treatment of osteoporosis in the United States. Dose is 2 g sachet nightly taken at bedtime, mixed with >30 ml of water at least two hours after food. Strontium ranelate has rarely been associated with venous thromboembolism and severe hypersensitivity reactions, including Stevens-Johnson syndrome and drug rash with eosinophilia and systemic symptoms. Patients should be advised to seek immediate medical advice if they develop a rash Teriparatide Teriparatide is a synthetic form of human parathyroid hormone, which acts by inhibiting bone resorption and increasing bone formation. Normally in response to low serum calcium, parathyroid hormone (PTH) is secreted from parathyroid glands, which acts to increase the concentration of calcium in serum by mobilizing calcium from bone. Pharmacologically, when PTH is administered intermittently at low doses, it has been shown to have predominantly anabolic effects on osteoblasts. PTH initiates bone formation first and only later promotes bone formation, which is indicated by bone turnover markers. Teriparatide is also indicated for use in men with a high-risk of fractures and where other treatments are unsuitable. Following a course of teriparatide it is recommended that patients use an antiresorptive medicine (e.g. a bisphosphonate) to further increase BMD and maintain the antifracture effect. Dose is 20 μg subcutaneous injection daily in the thigh or abdomen. Use is restricted to 18 month lifetime exposure (caused osteosarcoma in animal studies); informed consent is required. Transdermal teriparatide is also under development Hormone replacement therapy Hormone replacement therapy (HRT) was once considered a first-line therapy for the prevention and treatment of osteoporosis in women. Although HRT is not currently recommended for the treatment of osteoporosis, it is important to mention because many osteoporosis patients in a typical practice still use it for controlling postmenopausal symptoms. Data from the Women s Health Initiative confirmed that HRT can reduce fractures. However, the results were distressing with respect to the adverse outcomes associated with combined estrogen and progesterone therapy (e.g., risks for breast cancer, myocardial infarction, stroke and venous thromboembolic events) and estrogen alone (e.g., risks for stroke and venous thromboembolic events). 42 Drugs Under Clinical Development Cathepsin K inhibitors Cathepsin K is critical for normal osteoclastic bone resorption. The two agents, which are under development are balicatib (AAE581) and odanacatib (MK-0822). Clinical trials with these agents have demonstrated increase in hip and lumbar spine BMD, with a significant reduction in bone resorption markers. A newer highly potent cathepsin K inhibitor named relacatib is presently being studied in experimental animals. 43,44 Src kinase inhibitors Src kinase is a nonreceptor tyrosine kinase and a member of the Src family of protein kinases, which plays an important role in activity and survival of osteoclast cells. Osteopetrosis was caused in mouse due to Src inactivation, therefore it clearly indicated that Src is an important requirement for osteoclastic bone resorption. Saracatinib is a novel orally available competitive inhibitor of Src kinase shown to inhibit bone resorption in vitro. In a randomized, double-blind, placebo-controlled, multiple-ascending- dose Phase I trial, treatment with saracatinib inhibited osteoclastmediated bone resorption in healthy men without any significant adverse effects. The results of this study show that saracatinib has the potential to become an agent for the treatment of osteoporosis New SERMs Lasofoxifene: Lasofoxifene is a nonsteroidal SERM under development for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy. In a dose of 0.5 mg/day, the dose that is intended for clinical use, it was associated with a reduction in the risk of ER-positive breast cancer, major coronary heart disease events and stroke, although the numbers of these events were small in all groups. Lasofoxifene was significantly associated with the risk of venous thromboembolic events and pulmonary embolism. 48 Bazedoxifene: Bazedoxifene is a third-generation SERM under development for the prevention and treatment of postmenopausal osteoporosis. It is approved in the European Union (marketed in Italy and Spain) and is currently in the late phases of review by the US FDA. Bazedoxifene s combination with conjugated estrogens, Indian Journal of Clinical Practice, Vol. 23, No. 12, May

7 Aprela, is currently undergoing Phase III studies for the treatment of postmenopausal symptoms (including the prevention of postmenopausal osteoporosis/treatment of osteopenia). 49 Emerging therapy: The Wnt/β-catenin pathway regulates gene transcription of proteins important for osteoblast function. Study of the pathway has led to further discovery of inhibitors of Wnt signaling secreted by osteocytes. These include sclerostin and dickkopf1 protein (DKK1), both of which block binding of Wnt to LRP5 (lipoprotein receptor-like protein 5), thereby inhibiting osteoblast stimulation. Monoclonal antibodies designed to block the inhibiting action of both sclerostin and DKK1 are being considered for clinical trials based on promising results in animal models. Because both of these molecules appear to be secreted only by bone, it is hoped that they will have fewer systemic adverse effects. Therapies targeted at other molecules in the pathway, for example a small molecule inhibitor of GSK3β, the enzyme, which causes degradation of β-catenin in the absence of Wnt signaling, are considered less desirable targets due to their action in many tissues in addition to bone. 50 Nonpharmacologic Management Although pharmacologic approaches represent the cornerstone of treatment, some patients cannot comply with medication regimens, particularly because of potential adverse effects, but also because some patients cannot afford certain medication options or are not willing to take medications for prolonged time periods. For such patients nonpharmacologic management may be helpful. Bracing: 51 Bracing, or orthoses, such as thoracolumbar (mid to low back) braces are often prescribed for osteoporotic patients with vertebral compression fractures. Some braces are rigid and attempt to straighten the spine backward and are traditionally used in patients with an acute vertebral compression fracture. Fall prevention: 52 Falls in the elderly represent a significant cause of morbidity and mortality. Fall prevention involves environmental modifications, medication review, exercise, gait assessment and treatment, provisions for assistive devices and attention to concomitant conditions resulting in unsteady gait. Environmental modifications can consist of minimizing clutter, altering slippery surfaces and providing grab bars and other supports in tubs and near toilets. Multiple medications can have a key role in falls. Medication review should, therefore, be performed on a regular basis, with unnecessary and potentially harmful medications eliminated. Kyphoplasty: 53 Kyphoplasty is a minimally invasive spine procedure that involves the infiltration of bone cement into a fractured vertebral body after fracture reduction using a balloon tamp. Indications for this procedure include relatively acute, painful compression fractures refractory to conservative treatment. Kyphoplasty can result in diminished pain and reduce kyphosis; multiple studies have shown it to be an effective treatment for painful compression fractures with sustained improvements in back pain, back function and quality-of-life. References 1. Lirani-Galväo AP, Lazaretti-Castro M. Physical approach for prevention and treatment of osteoporosis. Arq Bras Endocrinol Metabol 2010;54(2): Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int 1992;2(6): Kanis JA, Johnell O, De Laet C, Jonsson B, Oden A, Ogelsby AK. International variations in hip fracture probabilities: implications for risk assessment. J Bone Miner Res 2002;17(7): Malhotra N, Mithal A. Osteoporosis in Indians. Indian J Med Res 2008;127(3): Mithal A, Dhingra V, Lau E; International Osteoporosis Foundation. The Asian Audit: epidemiology, costs and burden of osteoporosis in Asia IOP Publications, Available at 6. World Health Organization. WHO scientific group on the assessment of osteoporosis at primary health care level: summary meeting report. Available at int/chp/topics/osteoporosis.pdf. 7. Pande KC, Johansen KB, Helboe AB. Digital X-ray Radiogrammetry: Establishment and comparison of Indian Female and Male Normative Reference Data. J Bone Miner Res 2001;16:S Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 2005;115(12): Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med 2006;354(21): Lindsay R, Cosman F. Osteoporosis. In: Harrison s Principles of Internal Medicine. Faucy AS, Kasper DL, Longo DL, Hauser SL, Jameson JL, Loscajlo J, et al (Eds.), 18th edition, McGraw Hill Companies: New York 2012:p Osteoporosis. In: Current Medical Diagnosis & Treatment. 51st edition, Mcphee SJ, Papadakis MA, Rabow 848 Indian Journal of Clinical Practice, Vol. 23, No. 12, May 2013

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