Most doctors will prescribe these medications for 5-8 years, then consider taking their patients off the treatment as fracture risk remains low even after stopping the medication. Typically used for a short period of time earlier in menopause, due to long-term risks of breast cancer and blood clots. Use: It reduces the risk of broken bones in the spine, hips and other areas for high-risk men and postmenopausal women with osteoporosis. During therapy with an antiresorptive drug, such as a bisphosphonate, bone turnover is suppressed as evidenced by low serum or urinary levels of (fasting) N-telopeptide cross-links (< 40 nmol/L) or C-telopeptide cross-links. Osteoporosis is a condition that causes weak, porous bones. J Clin Endocrinol Metab, 2004. Weight-bearing exercise can help increase bone mineral density. Patients who have a significantly lower bone mineral density despite treatment should be evaluated for secondary causes of bone loss, poor drug absorption (if taking an oral bisphosphonate), and (except patients treated with IV bisphosphonates) drug adherence. Osteonecrosis of the jaw Medication-Related Osteonecrosis of the Jaw (MRONJ) Medication-related osteonecrosis of the jaw has no unanimously accepted definition or etiology but is generally held to be an oral lesion involving bare mandibular or maxillary bone present read more and atypical femoral fractures have been rarely reported in patients taking denosumab. combines your bone density test with other factors to estimate your risk of a fracture within the next 10 years. These fractures are most common among older patients, particularly those with read more, Greater trochanter Hip Fractures Hip fractures may occur in the head, neck, or area between or below the trochanters (prominences) of the femur. Loss of vertebral body height and increased biconcavity characterize vertebral compression fractures. Patients taking denosumab should not undergo a drug holiday because stopping this drug may cause a rapid loss in bone mineral density and, importantly, increase the risk of fractures, particularly vertebral fractures, sometimes multiple. Use for phrases In osteoporosis, there is an imbalance of these factors. These drugs are safe to use in patients with a creatinine clearance > 35 mL/minute. 89(7): p. 3261-9.. Oestrogen, of course, is made and secreted into the bloodstream some distance from bone and it also has profound effects on other tissues, such as the uterus and breast. Use: Prevents and treats osteoporosis in postmenopausal women, treats the disease in men and prevents additional broken bones for fracture patients with low bone density. [27]Robling, A.G., et al., Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. Understanding how bone remodelling is regulated is the key to the effective prevention and treatment of osteoporosis. The hypothesis that osteoporosis is a consequence of estrogen deficiency, has been proposed as early as 1941 by Albright and colleagues [1]. Delmas, Bone quality--the material and structural basis of bone strength and fragility. The mechanisms of bone loss may involve the following: Local changes in cytokine production, particularly involving cytokines such as receptor activator of nuclear factor kappa-B ligand [RANKL] that increase bone resorption by promoting differentiation and maturation of osteoclasts, Impaired formation response during bone remodeling, probably caused by age-related decline in the number and activity of osteoblasts, partly related to cytokine-mediated increases in the protein sclerostin, Other factors that affect bone resorption such as parathyroid hormone (PTH) and vitamin D. Idiopathic osteoporosis refers to the rare cases of fragility fractures in children, adolescents, premenopausal women, or men < 50 years with normal gonadal function and no detectable secondary cause, including in those with low bone mass (low Z-scores on dual-energy x-ray absorptiometry Dual-energy x-ray absorptiometry (DXA) Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. J Biol Chem, 2008. Endocrinology, 1998. Hyperparathyroidism can be differentiated when it causes subperiosteal resorption or cystic bone lesions (rarely). J Bone Miner Res, 2003. Learn more about the MSD Manuals and our commitment to Global Medical Knowledge. The sites of fracture are similar in primary and secondary osteoporosis. Osteoporosis, where bones become weaker and more likely to break, affects 3.5 million people in the UK - including . [29]Lacey, D.L., et al., Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. In osteoporosis, bone mass decreases, but the ratio of bone mineral to bone matrix is normal. 101(16): p. The balance between the activities of these two cell types governs whether bone is made, maintained, or lost. Although low bone mineral density (and the associated increased risk of fracture) can be suggested by plain x-rays, it should be confirmed by a bone mineral density measurement. The rate of bone loss can be slowed with drugs, but adequate calcium and vitamin D ingestion and physical activity are critical to maintaining optimal bone mineral density. Side effects: Risks vs. benefits should be discussed with a doctor. and P.H. Use DXA to measure bone mineral density in women 65 years; women between menopause and age 65 who have risk factors (eg, family history of osteoporosis, a low body mass index, and use of tobacco and/or drugs with a high risk of bone loss [including glucocorticoids]); men and women of any age who have fragility fractures; evidence on imaging studies of decreased bone mineral density or asymptomatic vertebral compression fractures; and patients at risk of secondary osteoporosis. Use: Prevents and treats osteoporosis in postmenopausal women and treats the disease in men, while reducing the risk of spine and hip fractures Form: Daily injection administered by the patient at home. Osteoporosis means that you have less bone mass and strength. Use: Treats osteoporosis in women who are at least 5 years past menopause and reduces the risk of spine fractures. Penninger, RANK-L and RANK: T cells, bone loss, and mammalian evolution. Suspect osteoporosis in patients who have fractures caused by unexpectedly little force (fragility fractures) of the spine, humerus, distal radius, or hip. The bone mineral content divided by area of bone (also measured in the DXA scan) is the bone mineral density in g/cm2. Further study to determine indications for these procedures is warranted. The 25-hydroxy vitamin D level should be 30 ng/mL. Bone biopsy is reserved for unusual cases (eg, young patients with fragility fractures and no apparent cause, patients with chronic kidney disease who may have other bone disorders, patients with persistently very low vitamin D levels suspected of having osteomalacia). Patients treated with IV bisphosphonates: Repeat DXA scan for monitoring after 3 years of therapy to help determine if treatment has been adequate or a longer therapy course is warranted. Romosozumab Antiresorptive drugs , the monoclonal antibody against sclerostin, has anabolic as well as antiresorptive effects. Diagnosis is by plain x-ray read more and pelvis Pelvic Fractures Pelvic fractures can involve the pubic symphysis, innominate bones, acetabulum, sacroiliac joint or sacrum. Typically read more , clavicle Clavicle Fractures Clavicle fractures are among the most common fractures, particularly among children. However, research over the last decades provided exiting new insights into mechanisms contributing to the onset of osteoporosis, which go far beyond this. The distal radius should also be scanned in a patient with hyperparathyroidism because this is the most common site of bone loss in hyperparathyroidism. [14]Van Pottelbergh, I., et al., Perturbed sex steroid status in men with idiopathic osteoporosis and their sons. (See also Overview of Fractures.) (See also Overview of Fractures.) Levels of fasting serum C-telopeptide cross-links (CTX) or urine N-telopeptide cross-links (NTX) reflect increased bone resorption. In patients with osteopenia, DXA should be repeated periodically to determine whether there is ongoing bone loss or development of frank osteoporosis requiring treatment. PMID: 9669137 DOI: 10.1016/s0889-8529(05)70004-9 Abstract As with many chronic diseases that express themselves late in life, osteoporosis is distinctly multifactorial, both in etiology and pathophysiology. 1999;149(16-17):454-62. Copyright 2023 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor read more , measurements of urinary free cortisol, and blood counts and other tests to rule out cancer, especially myeloma Diagnosis Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Bisphosphonates include the following: Alendronate (10 mg once a day or 70 mg orally once a week), Risedronate (5 mg orally once a day, 35 mg orally once/week, or 150 mg orally once a month), Ibandronate (150 mg orally once a month or 3 mg IV once every 3 months). In a DXA scan, the target areas, typically the spine and one or both hips, are imaged using x-rays of high and low energy (hence the term "dual energy"). Supplemental vitamin D is usually given as cholecalciferol, the natural form of vitamin D, although ergocalciferol, the synthetic plant-derived form, is also acceptable. It should also be considered in patients who fracture despite adequate antiresorptive therapy. Risk factors include invasive dental procedures, IV bisphosphonate use, and cancer. Penninger, 2023 International Osteoporosis Foundation, Factors influencing osteoclasts and osteoblasts, The role of genetics and environmental factors. Certain populations, including White and Asian people, have been thought to have a higher risk of osteoporosis than other groups. It's a result of when the heart is deprived of oxygen due to a lack of blood supply, which causes pain in the chest and, sometimes, the left arm. Osteoporosis is often called the silent disease because it may not cause symptoms. Nonvertebral fractures are typically symptomatic, but about two thirds of vertebral compression fractures are asymptomatic (although patients may have underlying chronic back pain due to other causes such as osteoarthritis). (See also Overview of Thoracic Trauma.) A cell surface receptor called RANK (for receptor activator of NFB) prods osteoclasts precursor cells to develop into fully differentiated osteoclasts when RANK is activated by its cognate partner RANK ligand (RANKL) [28]Yasuda, H., et al., Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. All men and women should consume at least 1000 mg of elemental calcium daily. Leslie WD, Majumdar SR, Morin SN, Lix LM: Change in bone mineral density is an indicator of treatment-related anti-fracture effect in routine clinical practice: A registry-based cohort study. 54(2): p. 186-99.. Then, after a brief reversal phase, during which the resorption pit is occupied by osteoblasts precursors, bone formation begins as progressive waves of osteoblasts form and lay down fresh bone matrix [9]Orwoll, E.S., Toward an expanded understanding of the role of the periosteum in skeletal health. Salmon calcitonin may provide short-term analgesia after an acute fracture, such as a painful vertebral fracture, due to an endorphin effect. However, a skeleton is alive and must be able to grow, heal, and respond to its environment. Diagnosis is by plain x-ray. With improved knowledge of the pathophysiology of osteoporosis, new targets for therapeutic intervention have been iden Previous data suggesting people with African ancestry achieve higher peak bone mass are currently being questioned. 1. Plain x-rays of the spine to look for asymptomatic vertebral fragility fractures should be considered in older patients with severe back pain and localized vertebral spinous tenderness and in patients who report > 3 cm height loss. Use: Increases bone density in the spine and hip and decreases fractures at both sites. After that, the loss slows down but continues. Cortical thickness and the number and size of trabeculae decrease, resulting in increased porosity. These procedures may reduce deformity in the injected vertebrae but do not reduce and may even increase the risk of fractures in adjacent vertebrae. There are three major backgrounds of osteoporosis in aged women: 1) the peak bone mass during their adolescence was low, 2) the bone loss by menopause due to estrogen deficiency was severe, and 3) the bone loss by ageing thereafter was severe (Figure 1); each of these has an independent mechanism. 3 Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria. There is evidence that fracture risk is increased in people taking non-steroidal anti-inflammatory drugs that inhibit COX-2 [20]Carbone, L.D., et al., Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. Osteoporosis is a disease that causes bones to become weak and brittle. 3597-602. When it does occur, your doctor can diagnose and treat it before it causes a broken bone. Educating patients about the risks of falls and fractures, instructing how to safely do daily activities, and modifying the home environment for safety also are important for preventing fractures. Collectively, estrogen . It is well established that oestrogen [11]Lindsay, R., Prevention and treatment of osteoporosis. If the FRAX score is above certain thresholds (in the US, a 20% probability of major osteoporotic fracture or 3% probability of hip fracture), drug therapy should generally be recommended. A low body mass index predisposes to decreased bone mass. Skeletal weakness leads to fractures read more ). Such symptoms can also come from other bone disorders or medical problems. 1 Learn more about the pathophysiology of osteoporosis, the pathways that regulate bone homeostasis, and how these pathways may contribute to osteoporosis. 115(12): p. 3318-25.. How these signalling molecules and various other endogenous (such as hormones) or external (such as diet and exercise) factors influence the cells involved in bone physiology is a topic of intense research activity. FRAX score. The immediate initiation of a bisphosphonate after an osteoporotic fracture has been controversial because of a theoretical concern that these agents may impede bone healing. 90(5): p. 3115-21.. There are limitations to the use of the FRAX score because it does not account for several factors, including history of falls or increased fall risk, the patient's bone mineral density at the lumbar spine, or family history of vertebral fractures. The balance of RANKL/osteoprotegerin may be crucial in osteoporosis. B. Boyle, and J.M. Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. Typically DXA is used; quantitative CT scanning can produce similar bone mineral density measurements but is currently not widely available. Women are 4 times more likely to develop osteoporosis. It also prevents bone loss during some breast and prostate cancer treatments. J Bone Miner Res, 2003. Oral bisphosphonates must be taken on an empty stomach with a full (8-oz, 250 mL) glass of water, and the patient must remain upright for at least 30 minutes (60 minutes for ibandronate) and not take anything else by mouth during this time period. The combination makes these bones strong and light, but flexible enough to absorb the stress from high impact exercises without breaking. Use: Prevents and treats osteoporosis in postmenopausal women while reducing the risk of spinal fractures Monitor response to treatment with DXA at appropriate intervals depending upon specific drug regimen used. The maternal mortality rate is higher in the US than in European countries (eg, Germany, Netherlands read more , or denosumab Antiresorptive drugs . Skeletal weakness leads to fractures with minor or inapparent trauma, particularly in the thoracic and lumbar spine, wrist, and hip (called fragility fractures). The exact mechanisms of this steroid hormone deficiency in postmenopausal women as well as in the elderly men are continuously being unraveled. Annu Rev Immunol, 2002. Osteoporosis is a "silent" disease because you may not have symptoms. Nondrug treatments include therapeutic exercise, heat, cold, electrical stimulation read more and massage Massage Treatment of pain and inflammation aims to facilitate movement and improve coordination of muscles and joints. However, it is not clear whether levels of bone turnover markers should be used as criteria for when to start or end a drug holiday. These fractures occur in the mid-shaft of the femur with minimal or no trauma and may be preceded by weeks or months of thigh pain. Please note that THE MANUAL is not responsible for the content of these resources. Osteoporosis. The FDA reviewed the medication in 2013 because there may be a 1 percent increase in skin cancers. The benefits of reduction of osteoporosis-related fractures far outweigh this small risk. These two cell surface receptors interact with a group of proteins in the cell called ITAM (immunoreceptor tyrosine-based activation motif) adaptor proteins to cause an increase in intracellular calcium. Fortunately, osteoporosis is preventable. However, use of estrogen increases the risk of thromboembolism and endometrial cancer and may increase the risk of breast cancer. Side effects: Oral bisphosphonates can cause upper stomach issues like heartburn. VFA is more likely to be useful in patients with height loss 3 cm. 31 minutes ago. Disk degeneration. This drug has been found to have a good safety profile at 10 years of therapy. If the parathyroid hormone is elevated it will cause osteoclasts to break down the bone in order to increase the calcium levels in the blood to correct the hypocalcemia. Use to remove results with certain terms J Clin Endocrinol Metab, 2004. Patients on a bisphosphonate holiday should be closely monitored for a new fracture or accelerated bone loss evident on a DXA scan, especially after being off therapy for 2 years or more. After stopping the medication, bone density and blood testing annually can help determine when and if more medication would be helpful. Osteoporosis is a major cause of disability in older women. The bones most often affected are the hips, spine, and wrists. Such scans are recommended for: Certain postmenopausal women, depending on risk factors, Certain men ages 50-69, depending on risk factors, Certain patients who have fractured a bone, depending on their background, Individuals on medications or with medical conditions that can affect bone density. In untreated patients, an increase in levels of bone turnover markers, particularly with higher levels, indicates an increased risk of fracture. Form: Injected by a doctor every six months. Chronic backache may be relieved by exercises to strengthen paravertebral muscles. Most cases occur in postmenopausal women and older men. TOP STORIES. Menopause. 93(2): p. 165-76.. RANKL, in fact, is produced by osteoblasts and is one of perhaps many signalling molecules that facilitate cross-talk between the osteoblasts and osteoclasts and help coordinate bone remodelling [30]Theill, L.E., W.J. Normally, bone formation and resorption are closely balanced. Learn about its causes, risk factors, and treatments. IV bisphosphonates are indicated if a patient is unable to tolerate or is nonadherent with oral bisphosphonates. Use: Treats postmenopausal women and men who are at high risk for fractures Osteoporosis may be triggered by various etiologies. Osteoporosis is a worldwide disease characterized by reduction of bone mass and alteration of bone architecture resulting in increased bone fragility and increased fracture risk. Vertebral fractures at T4 or above raise concern of cancer rather than primary osteoporosis. 2002, Academic Press: San Diego. Diagnosis is by dual-energy x-ray absorptiometry (DXA scan) or by confirmation of a fragility fracture. Raloxifene is a selective estrogen receptor modulator (SERM Selective estrogen receptor modulators (SERMS) Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. The risk of endometrial cancer can be reduced in women with an intact uterus by taking a progestin with estrogen (see Hormone therapy Hormone Therapy Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. By inhibiting bone resorption, bisphosphonates preserve bone mass and can decrease vertebral and hip fractures by up to 50%. In long bones, although the cortices may be thin, the periosteal surface remains smooth. So, add protein-rich foods such as lentils, tofu, fish, beans, eggs . The goals of prevention are 2-fold: preserve bone mass and prevent fractures. It reduces the risk of fractures of the hips, spine and other areas like the wrists and arms. The drug holiday is 1 year or longer. But there are other, locally produced signalling molecules that have profound effects on bone physiology. N Engl J Med, 2006. In addition, drug therapy is indicated for patients who already have osteoporosis or who have osteopenia if they are at increased risk of fracture, such as those with a high FRAX score, and patients taking glucocorticoids or aromatase inhibitors. An evaluation for secondary causes of bone loss should be considered in a patient with a Z-score -2.0. J Bone Miner Res 34(3):419-428, 2019. doi: 10.1002/jbmr.3622. The activities of these cells are also intimately intertwined. Form: Weekly pill, Drug: Risedronate Sodium More than 95% of osteoporosis in women and about 80% in men is primary and therefore without an identifiable underlying cause. Beginning with menopause, bone loss accelerates in women to about 3 to 5% a year for about 5 to 7 years and then the rate of loss decelerates. Avoiding heavy lifting can help. However, certain conditions may accelerate bone loss in patients with primary osteoporosis. DXA results are reported as T-scores and Z-scores. Although reliability varies for routine clinical use, elevated levels of CTX and NTX may be helpful in predicting fracture risk in an untreated patient, monitoring response to therapy, or with the timing of a drug holiday (2 Diagnosis references Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. If youre a woman who has gone through menopause or a man older than age 50, your doctor should follow National Osteoporosis Foundation guidelines and: Talk to you about your risk of osteoporosis and related fractures, Recommend a diet rich in fruits and vegetables that includes adequate vitamin D and calcium, with supplements prescribed as necessary, Recommend regular weight-bearing and muscle-strengthening exercises, Assess fall risk and offer appropriate preventions, Ask whether you smoke and how much alcohol you drink. regulation of systemic calcium and phosphate homeostasis and, equally important, of local bone remodeling processes. Most are minimally displaced and angulated. Patients with vitamin D deficiency may need even higher doses. These fractures are most common among older patients, particularly those with read more. Raisz, Chapter 54 - Prostaglandins and Bone Metabolism, in Principles of Bone Biology (Second Edition), J.P. Bilezikian, L.G. Estrogen deficiency causes bone loss, Family history of osteoporosis or fractures, Not eating enough fruits and vegetables for other nutrients (magnesium, potassium, vitamins C and K), Consuming too much alcohol, sodium or caffeine. Use: Prevents and treats osteoporosis in postmenopausal women and treats the disease in men, while reducing the risk of spine, hip and other broken bones While women are at higher risk for the disease, men can develop it, too. Some patients experience: Broken bones (mainly hips, spine or wrists), even from minor falls or bumps . This interaction sets off a complex chain of events within the cells, increasing osteoblast activity while at the same time interfering with osteoblast-osteoclast communication one of the ironies of bone remodelling is that the osteoblasts release factors that stimulate osteoclasts and drive bone resorption, as we shall see below. 2001, Academic Press: San Diego. Long-term bisphosphonate use may increase the risk of atypical femoral fractures. Form: Annual IV infusion, Side effects: Possible hot flashes and a small increased risk of blood clots, Drug: Raloxifene Typically used for prevention in postmenopausal women. Deficiency impairs bone mineralization, causing rickets in children and osteomalacia in adults and possibly contributing read more ). Hormones are possibly the most crucial modulators of bone formation. Theill, L.E., W.J. Form: Daily pill. Proc Natl Acad Sci U S A, 2004. Skeletal weakness leads to fractures read more ). Certain medications (prednisone, e.g.) These markers may remain low for 2 years off drug therapy. The frequency for follow-up DXA scanning varies from patient to patient, but some reasonable guidelines are as follows: Patients being treated with oral bisphosphonates: Repeat DXA scan usually after 2 to 3 years of therapy. Osteoporosis-related fractures most commonly occur in the hip, wrist or spine. Boyle, and J.M. View 3 more stories. However, after completion of a treatment course with an anabolic agent, the bone mineral density gains are quickly lost if a patient is not quickly transitioned to an antiresorptive agent such as a bisphosphonate Antiresorptive drugs . Secondary osteoporosis accounts for < 5% of osteoporosis in women and about 20% in men. Recent studies also suggest that sex hormone binding globulin (SHBG), which facilitates entry of oestrogen into cells, may also play a supportive role [17]Goderie-Plomp, H.W., et al., Endogenous sex hormones, sex hormone-binding globulin, and the risk of incident vertebral fractures in elderly men and women: the Rotterdam Study. This is where bone remodelling plays a crucial role. 229-38. Form: Nasal spray or injection, Side effects: Possible skin changes like rashes and eczema and a small increased risk of infection, Drug: Denosumab Insufficient dietary intake of calcium, phosphorus, magnesium, and vitamin D predisposes to bone loss, as does endogenous acidosis. 428(6984): p. 758-63.. The FDA has also approved a number of injections, IV infusions, tablets, nasal sprays and patches all shown to reduce fractures in randomized studies. For example, young adults with wider femurs might be at higher risk for hip fractures late in life because, on average, wider bones tend to have thinner cortical layers. Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, et al: One year of romosozumab followed by two years of denosumab maintains fracture risk reductions: Results of the FRAME Extension Study. Form: Commonly available as tablets or skin patches. Gonadal insufficiency is an important factor in both men and women; other factors include decreased calcium intake, low vitamin D levels Vitamin D Deficiency and Dependency Inadequate exposure to sunlight predisposes to vitamin D deficiency. Development of safer read more should take calcium citrate to maximize absorption. J Clin Invest, 2005. A few dietary and lifestyle changes to avoid osteoporosis include: 1. The following English-language resources may be useful. Studies suggest that among those 50 and older: Up to 1 in 2 women will break a bone due to osteoporosis equal to the risk of breast, ovarian and uterine cancer combined. Our doctors recommend treatments based on: Your age, overall health and medical history, The extent of the disease and your anticipated rate of bone loss, Your tolerance for specific medications, procedures or therapies. (See also Overview of Fractures.) Also, there is no reason to delay therapy in order to obtain a DXA scan because a hip or vertebral fragility fracture establishes the presence of osteoporosis. Acute back pain resulting from a vertebral compression fracture can be treated with short-term orthopedic support as needed, analgesics, and, when muscle spasm is prominent, moist heat Heat Treatment of pain and inflammation aims to facilitate movement and improve coordination of muscles and joints. Measures include, Smoking cessation Smoking Cessation Most smokers want to quit and have tried doing so with limited success. 139(7): p. 3178-84.. How any of these hormones impact bone remodelling depends on how they alter osteoclasts and/or osteoblasts activity. Affiliations 1 Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. N Engl J Med 377(15):1417-1427, 2017. doi: 10.1056/NEJMoa1708322, 5. Adv Ther 36(10): 28112824, 2019. doi: 10.1007/s12325-019-01063-9, Antiresorptive drugs (eg, bisphosphonates, hormone replacement therapy, a selective estrogen receptor modulator, receptor activator of nuclear factor kappa-B ligand [RANKL] inhibitor [denosumab]), Anabolic agents (eg, parathyroid hormone (PTH) analogues such as teriparatide and abaloparatide), Romosozumab, a monoclonal antibody against sclerostin with both antiresorptive and anabolic effects. Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Current osteoporosis therapies mitigate or reverse the loss of bone associated with age-related decreases of gonadal sex steroids, increase bone strength, and reduce fracture risk. Brought to you by Merck & Co, Inc., Rahway, NJ, USA (known as MSD outside the US and Canada) dedicated to using leading-edge science to save and improve lives around the world. Osteoporosis is a chronic condition characterized by excessive bone loss [1][2]. Residual pain may last for months or be constant, in which case additional fractures or underlying spine disorders should be suspected. Osteoporosis can be prevented by maintaining a diet that provides the essential vitamins and nutrients needed to strengthen bone structure. They also produce in this microenvironment proteolytic enzymes, among them cathepsin K, which dissolve bone matrix. 26(2): p. ER receptors are found on the surface of osteoblasts, as is oestrogen receptor-related receptor alpha (ERR), which may play an auxiliary role in regulating bone cells [16]Bonnelye, E. and J.E. The need for drug therapy Antiresorptive drugs is based on the probability of fracture, which is related to DXA results as well as other factors. Osteoblasts, through a yet poorly characterized mechanism, lay down new bone mineral. After this, bone loss occurs at a rate of about 0.3 to 0.5% a year. Bone is living tissue that is constantly being broken down and replaced. 1. Bone is lost at a rate of about 0.3 to 0.5% a year after age 40, in women accelerating after menopause to about 3 to 5% a year for about 5 to 7 years. Prostaglandins, particularly prostaglandin E2 (PGE2), stimulate both resorption and formation of bone [18]Pilbeam, C.C., J.R. Harrison, and L.G. A T-score < -1.0 and > -2.5 defines osteopenia. If necessary, physical therapists can evaluate a patient's gait and fall risk and help create safe individualized programs of core-strengthening exercises to help increase stability and decrease risk of falls. Most effective if started within 4 to 6 years of menopause, estrogen is given orally and may slow bone loss and possibly reduce fractures even when started much later. Current central DXA systems can also assess vertebral deformities in the lower thoracic and lumbar spine, a procedure termed vertebral fracture assessment (VFA). Romosozumab should not be initiated within 12 months of a patient having had a myocardial infarction or stroke. A fragility fracture is one that occurs after less trauma than might be expected to fracture a normal bone. The disease can affect anyone, but white and Asian women are most at risk. It has both antiresorptive and anabolic effects and has been shown to increase bone mineral density in the hip and lumbar spine and reduce fracture risk in postmenopausal women (3 Treatment references Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Oral bisphosphonates can cause esophageal irritation. Several factors appear to increase the risk of developing the disease: Gender. In fact, animal studies showed that increased production of osteoprotegerin leads to an increase in bone mass, while loss of the protein leads to osteoporosis and increased fractures [32]Bucay, N., et al., osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. In osteomalacia, the ratio of bone mineral to bone matrix is low. Introduction Osteoporosis, a disease characterised by low bone mass and microarchitectural deterioration of bone tissue is the most common chronic metabolic bone disease. Trabecular bone loss occurs more rapidly than cortical bone loss because trabecular bone is more porous and bone turnover is higher. Calcium intake should ideally be from dietary sources, with supplements used if dietary intake is insufficient. You may not even know you have the disease until you break a bone. Raloxifene may increase risk of thromboembolism. Appointments 216.444.2606. Enter search terms to find related medical topics, multimedia and more. Denosumab is a monoclonal antibody against RANKL (receptor activator of nuclear factor kappa-B ligand) and reduces bone resorption by osteoclasts. Early treatment of osteoporosis and osteopenia can ease pain, limit or halt bone loss, and prevent fractures. Delmas, Bone quality--the material and structural basis of bone strength and fragility. However, recent American Society of Bone and Mineral Research (ASBMR) treatment recommendations for secondary prevention of fractures are to start an oral bisphosphonate during the hospitalization for the fracture (2 Treatment references Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Vertebral deformities in the absence of trauma, even those clinically silent, are diagnostic of osteoporosis and are predictive of an increased risk of future fractures. We do not control or have responsibility for the content of any third-party site. Environmental factors can also have an enormous impact on bone physiology. Ask your doctor if you should get tested. Limiting alcohol intake to moderate use or less. Osteoporosis is most common in older women and people who have taken corticosteroids for long periods of time. Patients treated with anabolic therapy: Repeat DXA scan upon completion of therapy (2 years of teriparatide or abaloparatide, 1 year of romosozumab) to document improvement in bone mineral density with anabolic therapy and to establish a new baseline. 107(4): p. 513-23.. BMP receptors and LRP5 may cooperate to stimulate osteoblasts into action, though exactly how this might occur has not been clarified. Thoracic vertebral fractures may cause anterior wedging of the bone. Angina. Race. Clinicians should routinely ask about recent falls and otherwise assess fall risk Evaluation A fall is defined as a person coming to rest on the ground or another lower level; sometimes a body part strikes against an object that breaks the fall. Continual remodelling, and its effect on bone microarchitecture have a huge impact on the pathophysiology of osteoporosis. Fractures resulting from falls from a standing height or less, including falls out of bed, are typically considered fragility fractures. It has not been shown to reduce fractures. Globally, approximately 274 million women 50 years of age are expected to be at high risk of a fragility fracture by 2040. J Biol Chem, 2005. If and when denosumab is discontinued, transition to a bisphosphonate such as IV zoledronic acid should be considered for at least a year and longer if there is ongoing risk of fracture. Patients can get flu-like symptoms after the first dose of intravenous bisphosphonates. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary read more ) that may be appropriate for treatment of osteoporosis in women who cannot take bisphosphonates. Correa, Bone quality and osteoporosis therapy. Lorentzon M, Branco J, Brandi ML et al: Algorithm for the use of biochemical markers of bone turnover in the diagnosis, assessment, and follow-up or treatment of osteoporosis. Nature, 2004. Calcium supplements are taken most commonly as calcium carbonate or calcium citrate. The trusted provider of medical information since 1899, Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. 354(21): p. 2250-61. Because mechanical stress, including weight bearing, is necessary for bone growth, immobilization or extended sedentary periods result in bone loss. Osteomalacia may cause abnormalities on imaging tests similar to those of osteoporosis. As with denosumab, when romosozumab is discontinued, antiresorptive therapy should be given to prevent rapid bone loss. Osteoporosis can develop as a primary disorder or secondarily due to some other factor. 92(1): p. 4-8. and to a lesser extent testosterone directly or indirectly via the conversion into oestrogen [13]Seeman, E., The structural basis of bone fragility in men. Multiple thoracic compression fractures eventually cause dorsal kyphosis, with exaggerated cervical lordosis (dowagers hump). Vitamin D supplementation with 600 to 800 units a day is recommended. Even after a fracture, further problems are avoidable with the right steps. 12(9): p. 1260-8.. Inhibitors of RANKL have also shown promise as potential treatment for osteoporosis in humans. The Z-score corresponds to the number of standard deviations that the patient's bone mineral density differs from that of a person of the same age and sex and should be used for children, premenopausal women, or men < 50 years. Medication-Related Osteonecrosis of the Jaw (MRONJ), Maternal and perinatal mortality references, Selective estrogen receptor modulators (SERMS), Brought to you by Merck & Co, Inc., Rahway, NJ, USA (known as MSD outside the US and Canada) dedicated to using leading-edge science to save and improve lives around the world. They range from minimally displaced stable injuries caused by low energy falls to read more . There are several risk factors for postmenopausal osteoporosis, including a family history of osteoporosis, being thin or having a small frame, smoking, excessive alcohol consumption, a sedentary . J Bone Miner Res, 1997. 280(20): p. 19883-7.. Parathyroid hormone (PTH) and mechanical loading decrease the secretion of sclerostin by the oesteocytes [26]Bellido, T., et al., Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis.Endocrinology, 2005. However, loss of both types contributes to skeletal fragility. Oestrogen effects are mediated through one specific type of cell surface receptor called the oestrogen receptor alpha (ER), which binds and transports the hormone into the nucleus of the cell where the receptor-hormone complex acts as a switch to turn on specific genes. The tests presented in Tables 3 7 and 4 5 are appropriate for excluding secondary causes of osteoporosis. Monitoring for ongoing bone loss or the response to treatment with serial DXA scans should be done using the same DXA machine, and the comparison should use actual bone mineral density (g/cm2) rather than T-score. Treatments include antiresorptive drugs (eg, bisphosphonates, a selective estrogen receptor modulator, receptor activator of nuclear factor kappa-B ligand [RANKL] inhibitor, a drug used for hormone replacement therapy) or an anabolic agent such as teriparatide, abaloparatide, or romosozumab. Low body mass index or underweight The risk of developing osteoporosis increases as people grow older. Patients with weight loss should be screened for gastrointestinal disorders (eg, malabsorption Diagnosis Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Osteoporosis causes a loss of bone tissue in some women aged 50 and above. These two pathways may converge to activate a protein called the nuclear factor of activated T cells (NFAT) c1. Side effects: Possible calcium increases in the blood and urine and reactions at the injection site like itching and redness. Stress fractures do not usually result from a discrete read more are not considered osteoporosis-related fractures. [Pathophysiology of osteoporosis] Wien Med Wochenschr. Make sure to discuss possible side effects with your doctor. 1068: p. 173-9. It is the most common reason for a broken bone among the elderly. More than 95% of osteoporosis in women and about 80% in men is primary. However, as we age, daily remodelling leads to a gradual resorption of the minerals on the inside of the cortical layer and in the bone cavity itself leads to an inexorable loss of trabecular bone and a widening of the bone cavity. Form: Monthly pill or IV infusion every 3 months, Drug: Zoledronic Acid Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats) read more , celiac disease Diagnosis Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption read more , inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal read more ) as well as cancer. Your body regularly replaces the components of your bones. Always consult your doctor for a diagnosis. Bones show decreased radiodensity and loss of trabecular structure, but not until about 30% of bone has been lost. 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