Risedronate and ibandronate oral and i. Numerous studies have been conducted with these and other bisphosphonates that demonstrate a beneficial effect on inhibiting bone loss and, in some cases, reducing fracture risk. Bisphosphonate therapy is designed to prevent or slow the rate of bone loss in patients receiving cancer treatment to reduce fracture risk. Initiation of therapy earlier, prior to the occurrence of severe osteoporosis or fracture, rather than later may therefore be more effective.
This is supported by results from the Zometa-Femara Adjuvant Synergy Trial Z-FAST in which zoledronic acid was evaluated for prevention of cancer therapy-related bone loss in postmenopausal women with early breast cancer who were receiving adjuvant letrozole therapy. Zoledronic acid 4 mg i. Upfront treatment with this bisphosphonate increased BMD as early as 6 months after initiation of therapy, whereas delayed administration resulted in decreased BMD Fig.
Upfront administration of zoledronic acid to premenopausal women with breast cancer increased bone mineral density BMD in the lumbar spine and hip at 6 months after initiating therapy compared with delayed administration. While both oral and i. Some agents can reduce skeletal-related events SREs , prolong time to first SRE, and alleviate pain in women with metastatic breast cancer receiving chemotherapy or endocrine therapy and men with metastatic prostate cancer receiving ADT.
The i. However, only zoledronic acid has been shown to significantly increase BMD over baseline in this patient population Fig. Longer survival has not been demonstrated with any bisphosphonate. Change from baseline in bone mineral density at the lumbar spine, femoral neck, trochanter, and total hip in men with nonmetastatic prostate cancer receiving androgen deprivation therapy.
Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. Effective management of bone loss is key for patients who experience osteoporosis resulting from their malignancy and cancer therapy. This can be divided broadly into two categories: improving bisphosphonate therapy by increasing compliance and reducing toxicity, and lifestyle modifications that help reduce bone loss and fracture risk.
The toxicity profile of oral bisphosphonates differs from that of their i. Oral bisphosphonates are often limited by their pharmacodynamics and toxicity in the gut. Absorption can be further decreased if these agents are not taken exactly as prescribed. High doses can cause significant GI toxicities, including esophageal and gastric ulcers, esophagitis, and nausea.
However, oral bisphosphonates can be administered at home in weekly or monthly formulations, offering convenience for patients [ 48 ]. Intravenous bisphosphonates are generally well tolerated, although transient flu-like symptoms, such as nausea, myalgia, arthralgia, and low-grade fever, and increased bone pain can occur [ 48 ]. Approximately one third of patients experience such symptoms, usually following the first infusion. These typically resolve over several hours to days, and may respond to acetaminophen or low-dose steroids.
Acute renal toxicity has occurred following rapid infusion of i. Increases in serum creatinine levels are usually not of clinical significance. Given the potential for renal toxicity, monitoring of serum creatinine levels is recommended at baseline and prior to drug infusions [ 30 , 48 ]. Pamidronate and zoledronic acid are not indicated for cancer patients with severe renal impairment i. The safety of bisphosphonates in patients with pre-existing renal insufficiency has not been fully evaluated.
Multiple cycles of therapy could lead to progressive renal deterioration and renal failure with the need for subsequent dialysis. Physicians should consider the potential risks and benefits of continuing bisphosphonate therapy in patients with hypercalcemia of malignancy who exhibit severe renal impairment. Other risk factors that may affect renal toxicity of bisphosphonates include dehydration and the use of other nephrotoxic drugs [ 52 ].
Osteonecrosis of the jaw ONJ was first reported in as a complication in patients with metastatic cancer or multiple myeloma treated with nitrogen-containing bisphosphonates [ 54 ]. The following year a retrospective chart review of patients at Memorial-Sloan Kettering Cancer Center identified 13 patients with these diseases who had been treated with i. The only prospective study of ONJ in patients with multiple myeloma or metastatic breast or prostate cancer was published in by Bamias et al.
These authors reported an overall incidence of 6. ONJ was significantly more common in patients receiving zoledronic acid than in those treated with pamidronate. Most patients presenting with ONJ in these three studies had been treated with chemotherapy, radiation therapy, or steroids, had experienced oral trauma, or had experienced recent or existing periodontal problems such as extraction or infection [ 54 — 56 ]. Of note, all affected patients had either multiple myeloma or metastatic breast cancer, with no ONJ occurring in the settings of other metastatic solid tumors, osteoporosis, or hypercalcemia of malignancy.
Higher doses and longer duration of treatment, dental extractions, and periodontal disease were identified as risk factors. Older age was also found to be a significant risk factor in a retrospective review of 90 patients with multiple myeloma [ 58 ]. An expert panel of oral and maxillofacial surgeons, endocrinologists, and medical oncologists was convened to identify risk factors and propose clinical guidelines for managing ONJ [ 59 ].
The report of this group, and a similar position paper of the American Academy of Oral and Maxillofacial Pathology [ 60 ], concluded that its true incidence cannot be accurately determined from the retrospective reviews and case reports published to date. This information, as well as causal factors related to this adverse event, is the subject of large ongoing prospective trials. To safeguard against ONJ, patients should alert dental professionals that they are initiating bisphosphonate therapy. A thorough oral exam is recommended prior to initiating treatment, and good oral hygiene should be stressed.
Any dental procedures and major debridement surgeries should be postponed if possible. ONJ is best managed through conservative measures such as antibiotics and chlorhexidine mouth rinses. Increased awareness of this risk during bisphosphonate therapy and early diagnosis of ONJ may reduce the morbidity associated with such complications [ 59 , 60 ]. Compliance is a potential barrier to effective use of oral bisphosphonates. Long-term, consistent adherence to prescribed therapy is essential for patients to realize the full benefits of treatment.
Poor compliance is not uncommon, however, and can result in early discontinuation of therapy and reduced efficacy. Tosteson et al. Additionally, some patients have difficulty swallowing the capsules or following complex dosing procedures required to minimize GI toxicity e. Despite these potential barriers, oral bisphosphonates are successfully taken by many women and men with postmenopausal or age-related osteoporosis. Better education of patients and health care professionals regarding the importance of good compliance with oral bisphosphonate therapy and its impact on efficacy and toxicity will help to maximize patient outcomes.
In addition to bisphosphonate therapy, other nonpharmacologic interventions can help improve bone health with the aim of reducing fracture risk in patients receiving cancer therapy. A proper diet will ensure that protein consumption is sufficient for maintaining muscle strength and body weight, and that intake of essential vitamins and minerals is adequate. Because calcium and vitamin D are key for bone formation and maintenance, patients should be counseled possibly by a registered dietitian to obtain foods rich in these nutrients and have adequate sunlight exposure for vitamin D production [ 29 ].
For patients unable to reach the daily target levels of calcium and vitamin D, bioavailable supplements are an option. Any supplemental calcium should be taken in divided doses to improve absorption. Routine monitoring of serum levels of hydroxyvitamin D 25OHD; the primary metabolite of vitamin D may identify vitamin D deficiencies and facilitate prompt intervention [ 64 ]. All patients on bisphosphonate therapy should have routine assessment of their vitamin D status. A regular exercise program can help improve bone strength and mobility in cancer patients at risk for bone loss.
Both weight-bearing aerobic exercise e. Such a program will increase bone health and strength, improve overall well-being and quality of life, and decrease the incidence of falls that may lead to fracture. Other lifestyle changes that can improve bone health include smoking cessation and avoidance of excessive alcohol and caffeine [ 65 ]. Current studies are investigating new avenues for improving diagnosis, prognosis, and treatment for patients experiencing bone loss related to cancer therapy.
These include analysis of circulating biomarkers of bone metabolism, high-resolution MRI, and alternate bisphosphonate dosing schedules. Changes in levels of biochemical markers associated with bone metabolism may have prognostic utility in the management of osteoporosis for patients with cancer. Therapies that cause hypogonadism result in increased bone turnover, and biochemical markers of bone formation and bone resorption can be detected in the serum and urine of cancer patients with bone metastases [ 26 , 66 , 67 ].
Several studies in malignant bone disease have demonstrated that high urinary levels of the bone resorption marker NTx are correlated with poorer outcome, including a higher risk for fracture and other SREs, greater risk for disease progression, as well as a four- to sixfold greater risk for death [ 68 — 70 ].
Bone biomarkers, therefore, may be useful for predicting skeletal complications, although their value in the diagnosis of bone metastases or other SREs has not yet been determined. Several markers of bone resorption and formation are currently being evaluated as useful surrogate markers for monitoring response to bisphosphonates in the premetastatic setting. This powerful method is being developed to provide three-dimensional imaging of bone, providing full tissue disclosure rather than information based on a limited tissue sample. As a result of the complexity of oral dosing regimens, poor compliance, and toxicity that can limit daily or weekly administration of oral bisphosphonates, other schedules relying on intermittent or extended dosing are being investigated [ 72 ].
Monthly or intermittent administration of oral ibandronate was shown to be at least as effective as daily therapy in women with postmenopausal osteoporosis, with similar gains in BMD [ 73 , 74 ]. Extending this further, the effects of once-yearly zoledronic acid on BMD and bone turnover were found to be equivalent to an everymonth regimen [ 75 ]. Ongoing trials are evaluating whether this yearly dosing regimen can also reduce fracture risk in patients with osteoporosis. Patients with cancer are at significant risk for bone loss and fracture, not only from their disease and age-related osteoporosis but also from therapy for their malignancy.
A variety of anticancer treatments induce or exacerbate bone loss, which has been shown to occur in hormone-sensitive tumors and other cancers. This loss of bone density has serious clinical consequences, increasing the risk for fracture and other morbidities that can in turn decrease survival. Unfortunately, low awareness of this problem and infrequent screening result in many cancer patients with undiagnosed bone loss. Thus, significant decreases in BMD may occur well before osteoporosis per se is manifested or before fracture is detectable.
Recognition of the magnitude of this problem and early identification of patients at risk for bone loss are key to effective management. Because cancer therapy-associated bone loss is largely preventable, an aggressive approach to bone health is critical. Preserving BMD should be an important concomitant goal of cancer therapy and not simply considered as supportive care. High-risk patients should have early and regular assessment of BMD and risk factors for bone loss, with implementation of bisphosphonate therapy where indicated.
Women’s Wellness: Bone density in women – Mayo Clinic News Network
Patients also need to be educated and empowered to take an active role in promoting bone health through better diet, supplementation, exercise, and other positive lifestyle changes. Such a proactive rather than reactive approach to bone health will help to maintain BMD, minimize fracture risk, and improve outcomes and quality of life in patients receiving cancer therapy.
User Name Password Sign In. Guise, M. Accepted August 25, L earning O bjectives After completing this course, the reader will be able to: Identify cancer therapies associated with bone loss. Explain the unique aspects of cancer therapy—associated bone loss. Screen for and manage bone loss in cancer patients. Describe the safety profile of bisphosphonate drug treatment. Previous Section Next Section.
View this table: In this window In a new window. Table 1. Figure 1. Table 2. Figure 2. J Bone Miner Res ; 15 : — CrossRef Medline Google Scholar. Figure 3. Figure 4. J Urol ; : — Safety The toxicity profile of oral bisphosphonates differs from that of their i. Compliance Compliance is a potential barrier to effective use of oral bisphosphonates. Lifestyle Modifications In addition to bisphosphonate therapy, other nonpharmacologic interventions can help improve bone health with the aim of reducing fracture risk in patients receiving cancer therapy.
Bone Biomarkers Changes in levels of biochemical markers associated with bone metabolism may have prognostic utility in the management of osteoporosis for patients with cancer. Alternate Bisphosphonate Dosing Regimens As a result of the complexity of oral dosing regimens, poor compliance, and toxicity that can limit daily or weekly administration of oral bisphosphonates, other schedules relying on intermittent or extended dosing are being investigated [ 72 ].
Previous Section. Pfeilschifter J, Diel IJ. Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol ; 18 : — Higano CS. Kim, M-S. Ginseng for managing menopause symptoms: A systematic review of randomized clinical trials. Journal of Ginseng Research , 37 1 , Menopause and menopause treatments [Fact sheet]. Montemuro, S. Relieving the symptoms of menopause: From herbs to hormones. British Columbia Medical Journal , 43 8 , Osteoporosis [Fact sheet]. Vitamin D [Fact sheet].
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Please note: If no author information is provided, the source is cited instead. Latest news Exercise may increase lifespan 'regardless of past activity levels'. New research finds that becoming more active significantly lowers a person's death risk, regardless of how active they have been in the past. Morning people may have lower breast cancer risk. A large study of women found that those with a morning preference were less likely to have or develop breast cancer than those with an evening preference.
Obesity: How diet changes the brain and promotes overeating. In a study in mice, researchers found that neurons that normally signal to the brain to stop eating are less active in obese animals. They include alcoholism, diabetes, rheumatoid arthritis, thyroid imbalances, liver or kidney disease, Crohn disease, celiac disease, and anorexia nervosa. Women are much more likely to develop osteoporosis than men.
Men start with higher bone density and lose calcium at a slower rate than women, which is why their risk is lower. Nevertheless, older men are also at risk for osteoporosis. As people age, their risks for osteoporosis increase. Aging causes bones to thin and weaken. Osteoporosis is most common among postmenopausal women, and screening for low bone density is recommended for all women over age Although adults from all ethnic groups are susceptible to developing osteoporosis, white and Asian women and men face a comparatively greater risk. Osteoporosis is more common in people who have a small, thin body frame and bone structure.
Low body weight less than pounds or a BMI less than 21 is a risk factor for osteoporosis. Osteoporosis tends to run in families. People whose parents had a fracture due to osteoporosis are themselves at increased risk for osteoporosis. Estrogen deficiency is a primary risk factor for osteoporosis in women.
Estrogen deficiency is associated with:. Low levels of testosterone increase osteoporosis risk. Certain types of medical conditions hypogonadism and treatments prostate cancer androgen deprivation can cause testosterone deficiency. Diet plays an important role in both preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies are risk factors for osteoporosis. The body requires adequate vitamin D in order to absorb calcium. In the United States, many food sources of calcium, such as milk, are fortified with vitamin D. Lack of weight-bearing exercise and a sedentary lifestyle increase the risk for osteoporosis.
People who are chair-bound or bedbound due to medical infirmities and who do not bear weight on the bones are at risk for osteoporosis. Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract, and is the essential companion to calcium in maintaining strong bones.
The maximum density that bones achieve during the growing years affects whether a person goes on to develop osteoporosis. People, usually women, who never develop adequate peak bone mass in early life are at high risk for osteoporosis later on. Exercise and good nutrition are very important during the first three decades of life, when peak bone mass is gained. They are excellent safeguards against osteoporosis and other health problems.
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Low bone density increases the risk for fracture. Bone fractures are the most serious complication of osteoporosis. Spinal vertebral fractures compression fractures are the most common type of osteoporosis-related fracture, followed by hip fractures, wrist fractures, and other types of broken bones.
Compression fractures can occur, without falling, from even everyday motions such as bending or turning. Hip fractures, in addition to causing disability, can increase the risk of early death. Complications of hip fractures include hospital-acquired infections and blood clots in the lungs. Osteoporosis is usually asymptomatic until a fracture occurs, so bone density testing is important.
A fracture of the spine, wrist, or hip is often the first sign of osteoporosis. These fractures can occur even after relatively minor trauma, such as bumping into an object or falling from a standing position. They can also occur from simple movements such as reaching, turning, or bending over. Compression fractures occur in the vertebrae of the spine as a result of weakened bones.
These fractures can occur suddenly, most commonly near the waistline or just above or below it. Compression fractures may be mistaken for arthritis or the aches and pains of aging. Often, they are discovered when x-rays of the spine are done for other reasons. A bone density test can help your health care provider detect osteoporosis and predict your risk for bone fractures.
Testing is important because osteoporosis can occur with few or no symptoms. There is not full agreement on whether men should undergo this type of testing. Some groups recommend testing of men at age 70 while others state that the evidence is not clear enough to say whether men at this age benefit from screening. Younger women, as well as men of any age, may also need bone density testing if they have risk factors for osteoporosis. These risk factors include:. Bone densitometry is a test for measuring bone density and predicting fracture risk. DXA is simple and painless and takes 2 to 4 minutes.
It uses low-dose x-rays. You lie on a soft table while the scanner passes over your lower back and hip. The test measures concentrations of calcium and other bone minerals in these areas. You should not take any calcium supplements in the 24 hours before the test. A radiologist a doctor specially trained to interpret imaging tests will review the results of the test and send a report to your health care provider. Central DXA measures the bone mineral density at the hip, upper thigh bone femoral neck , and spine.
Other tests may be used, but they are not usually as accurate as DXA. Screening tests using these technologies are sometimes given at health fairs or other non-medical settings. These screening tests typically measure peripheral bone density in the heels, fingers, or leg bones. The results of these tests may vary from DXA measurements of the spine and hip. While these peripheral tests may help indicate who requires further BMD testing, a central DXA test is required to diagnose osteoporosis and to monitor treatment response.
Osteoporosis is diagnosed when bone density has decreased to the point where fractures can result from mild stress, the so-called fracture threshold. This is determined by measuring bone density and comparing the results with the norm, which is defined as the average bone mineral density in the hipbones of a healthy year-old adult. The doctor then uses this comparison to determine the standard deviation SD from this norm.
Standard deviation results are given as Z and T scores:. The lower the T-score, the lower the bone density, and the greater the risk for fracture. In general, doctors recommend beginning medication when T-scores are People who have other risk factors may need to begin medication when they have osteopenia scores between -1 and Osteopenia refers to bone mineral density that is lower than normal, but not low enough to be classified as osteoporosis.
Osteopenia is considered a precursor to osteoporosis. Doctors don't yet know the best testing schedule for people whose first test does not reveal osteoporosis. Current practice recommends that older people have a bone mineral density test every 2 years. However, some recent research suggests that low-risk women who have normal test results may be able to wait for up to 15 years to be rescreened. Women at higher risk would need to have another test at much shorter intervals. Discuss with your doctor how often you should be tested based on your individual risk factors.
In certain cases, your health care provider may recommend that you have a blood test to measure your vitamin D levels. A standard test measures hydroxyvitamin D, also called 25 OH D. Depending on the results, your provider may recommend that you take a vitamin D supplement if you are at high risk for fractures. There is currently no consensus on what levels of vitamin D indicate deficiency, or what the optimal levels should be. Healthy lifestyle habits, including adequate intake of calcium and vitamin D, are important for preventing osteoporosis and supporting medical treatment.
A combination of calcium and vitamin D may reduce the risk of osteoporosis. For strong bones, people need enough of both calcium and vitamin D. The best sources are from calcium-rich and vitamin D-fortified foods. Certain types of foods can interfere with calcium absorption. These include foods high in oxalate such as spinach and beet greens or phytate peas, pinto beans, navy beans, wheat bran. Diets high in animal protein, sodium, or caffeine may also interfere with calcium absorption. Doctors are currently reconsidering the use of calcium and vitamin D supplements based on studies suggesting that supplements do not make much difference in bone mineral density protection.
The U. According to the USPSTF, taking daily low-dose vitamin D supplements less than IU , with or without calcium supplements less than 1, mg , does not prevent fractures. In addition to possible lack of benefit, these supplements are associated even at lower doses with certain risks, like kidney stones.