Mention the word “steroids” and most people think of body builders trying to bulk up their muscles or professional athletes such as Major League Baseball players such as Alex Rodriguez, who confessed to using performance-enhancing drugs. “Great,” you might think, “I'll take steroids to look buff.” Unfortunately, instead of building muscle, the antiinflammatory type of steroids, such as prednisone, can lead to muscle and bone loss.
These are called corticosteroids or glucocorticoids, in contrast to the “anabolic steroids” that athletes sometimes abuse. “Glucocorticoid-induced osteoporosis” is the most common type of osteoporosis after postmenopausal osteoporosis or age-related causes. You may also see the term “GIOP” used for short. For simplicity's sake, the less formal “steroids” will be used to refer to glucocorticoids in this chapter.
Steroids are given to millions of people to counteract allergic or inflammatory conditions. Common problems treated with steroids include lung problems (such as asthma or emphysema), rheumatoid arthritis, and severe psoriasis.
What Are the “Steroids”?
Steroids are usually referred to by their generic name. Selected brand names are also listed just in case your pill bottle or packet is labeled by brand. The most common glucocorticoid steroid is prednisone. Other common oral steroids are shown in the table below with the dose that corresponds to 5 mg of prednisone.
STEROIDS: BONE LOSS AND INCREASED FRACTURE RISK
Mechanism of Harmful Effects on Bone
Steroids affect bone through multiple pathways. Bone loss is primarily due to the effect of steroids on osteoblasts. Steroids decrease the birth rate of osteoblasts, suppress their activity, and cause earlier death of the osteoblasts. Initially, these bone-breakdown cells increase in number and activity.
Other effects of steroids include decreased production of estrogen and testosterone, decreased calcium absorption from the small intestine, and increased loss of calcium in urine. Muscle loss and weakness may occur with long-term use. As a consequence, there is increased risk of falls. Falls, in turn, increase the risk of fractures independent of bone loss.
Steroids are powerful medicines that are useful in many situations. The downside includes a multitude of side effects. Bone is one of the places where steroids are harmful. Individual responses to steroids are variable. One's sensitivity to steriods may be related to the dose of steroids, the duration of use, the disease or problem treated, age, and hormonal status. Postmenopausal women are at highest risk for steroid-induced osteoporosis.
Bone loss with steroids use is most marked in the spongy trabecular bone sites, like the lumbar spine, wrist, and ribs. Steroids also affect the hip and other sites of dense cortical bone. Steroid therapy is associated with early, rapid bone loss within the first few months up to six months, followed by a more gradual but constant decline. Bone density loss is dose-related and may be accentuated in the presence of other risk factors for osteoporosis.
The typical pattern of bone loss during the first year of therapy is 8 to 12 percent at the spine and 2 to 3 percent at the hip when the average dose is 7.5 mg per day of prednisone. In subsequent years, the annual decline is less. Practically, no dose is without negative side effects. However, the amount of bone loss is related to the daily dose of steroids. Bone loss increases markedly for doses over 20 mg of prednisone per day.
Initially, bone turnover may be increased due to an increase in the number and activity of osteoclasts. It is followed by a reduction in bone turnover after the first six to twelve months of steroid therapy, which is reflected in the pattern of bone loss. Bone formation is decreased due to the negative impact of steroids on osteoblasts. As a result, thinning of bone structure with steroids exceeds the thinning observed in those with postmenopausal osteoporosis, who have normal bone formation.
It is important to realize that among steroid-treated individuals fractures occur at a higher level of bone density than is seen in postmenopausal osteoporosis. This reflects changes in bone structure and quality as well as bone mass. Steroids affect osteocyte viability and induce the disruption of the osteocyte network. Since osteocytes play an important role in the maintenance of bone quality, this is thought to contribute to increased bone fragility and the risk of fractures at higher levels of bone mineral density. Therefore, the risk of fracture may be underestimated by using results of DXA alone.
Fracture risk may increase within three months of starting steroids. Spine fractures are the most common. However, the majority of these are silent with no symptoms. Even doses of prednisone less than 2.5 mg per day increase the risk of spine fractures by 50 percent. Doses of prednisone over 7.5 mg per day increase fracture risk by 500 percent. In general, the rate of spine fractures is increased four- to fivefold and the rate of hip fracture is increased twofold.
The FRAX calculator includes steroid use in its estimation of ten-year fracture risk. This is applicable only to men and women ages forty to ninety. The absolute risk of fracture in premenopausal women and younger men is generally low unless a fracture has already occurred. Since the FRAX calculation uses bone density of the hip rather than the spine measurement, and the spine is where dramatic bone loss may occur, it may underestimate your fracture risk. Your doctor must take into account your dose of steroids and be very aware of the bone risk involved.
After stopping steroid therapy, some but not all of the lost bone may be added back. However, the fracture risk does not return to pretreatment levels, though it will be lower than it was during steroid treatment.
When steroids are used at high doses or for long periods of time, loss of muscle mass may occur. As a result, the risk of falls increases and this leads to an increased risk of fractures independent of bone density.
INHALED STEROIDS: “MAYBE” BONE LOSS
The chronic use of inhaled steroids may cause bone loss. Inhaled steroids are less likely to have the effects of oral steroids. However, in higher doses and for long periods, enough may be absorbed to harm the bone. Lower bone density measurements at the spine, hip, and forearm have been observed in studies that compared users of inhaled steroids to nonusers. However, it may be hard to separate the effects of underlying disease and previous use of oral steroids from the effects of inhaled steroids.
Inhaled steroids are commonly used for asthma and emphysema or COPD (chronic obstructive pulmonary disease). The largest clinical trial to investigate inhaled steroids and bone was part of the Towards a Revolution in COPD Health (TORCH) study. No difference in bone density or fractures was observed between placebo sprays and inhaled therapies after three years of use. However, the researchers' main concern was that the majority of participants, both men and women, had low bone density.
If you have chronic lung disease and use steroid inhalers, a measurement of bone density along with an evaluation of your risk factors for fracture should be done. Even if the inhalers are not causing problems, your lung disease or previous use of steroids may be.
NASAL STEROIDS: NOT WITH USUAL DOSES
Limited data is available for nasal steroids. Only a few cases have been reported in the literature. Dr. Angelo Licata, an endocrinologist at the Cleveland Clinic in Cleveland, Ohio, reported on a forty-eight-year-old postmenopausal woman with nasal allergies who used her nasal steroid spray more frequently than prescribed. Over one year, she lost 10 percent of bone density at the spine and 5 percent at the hip despite being on estrogen therapy. In addition, she had other physical findings that raised suspicion about excess use of steroid spray. Whether these effects were from increased nasal absorption or from swallowing the excess liquid spray was unclear.
Using nasal steroids as prescribed does not appear to produce harmful effects on bone.
BONE PROTECTIVE THERAPY
The lowest possible dose is always desirable when it may not be an option to completely stop steroids. Decrease or eliminate all other risk factors, such as excessive alcohol use and smoking. General measures should include adequate calcium and vitamin D intake, a regular exercise program, and taking steps to reduce the risk of falling. However, for many patients taking steroids, these measures are not enough. Because many variables come into play, you must be attentive to your bone health while on steroids.
As seen in several clinical trials, subjects in the placebo groups who took calcium plus vitamin D had less bone loss than expected. Vitamin D blood levels need to be monitored, since steroids may decrease absorption. Higher doses of vitamin D supplements may be required to maintain levels above 30 ng/ml.
Four of the osteoporosis medicines have been tested in steroid users and approved by the FDA for this indication. The diverse group of individuals taking steroids complicates treatment studies. Studies combine adult men and women of all ages with different diseases who are taking different medicines in a variety of doses. Most of the clinical trials studied postmenopausal women with smaller numbers of premenopausal women and men included.
Use of osteoporosis medicines for steroid users is classified into two types:
- Prevention: For individuals who are at risk for loss of bone as a result of beginning treatment with steroids.
- Treatment: For individuals who have lost bone due to long-term steroid therapy.
In general, the steroid studies enroll smaller numbers of subjects and bone density changes are the main outcome, not fractures. Prevention studies are usually twelve months in duration and focus on prevention of bone loss. Treatment studies may be up to three years in length. Due to the smaller number subjects, few fractures are observed.
BISPHOSPHONATES AND FORTEO
The two most common medicines used are generic alendronate (Fosamax) and Actonel. In steroid-treated patients, these agents increase bone density at the spine by 3 to 4 percent compared with placebo over one year. These agents also decrease the risk of spine fractures.
Reclast is gaining in popularity because it does not interfere with oral medicines and is given by vein only once a year. This is helpful for steroid users because, on average, people on steroids take a total of six to eight different medicines.
Forteo is also an appealing choice because it counters the effects of steroids on bone formation. Forteo directly stimulates the osteoblasts and inhibits their breakdown, which may reverse the key effects of steroids on bone formation. Forteo improves both bone density and bone quality, which results in rebuilding microstructure.
One three-year study compared Forteo and Fosamax at 10 mg a day in over four hundred high-risk patients who were taking long-term steroids. Bone density increased in patients receiving either Forteo or Fosamax. However, patients receiving Forteo had larger increases in BMD and fewer new spine fractures. Therefore, Forteo should be considered as a first-line therapy in high-risk patients.
FDA-Approved Medicines to Prevent Bone Loss from Steroids
The addition of an osteoporosis drug may be necessary for preventing bone loss while you are taking steroids. Clinical trials evaluated these drugs in men and both premenopausal and postmenopausal women using oral steroids. The FDA has approved the following drugs for the indication of “glucocorticoid-induced osteoporosis.” You may also see the term “GIOP” used for short.
As long as you are taking steroids, therapy with osteoporosis medicines will prevent bone loss. If you are on long-term steroids but discontinue bone-protective therapy, you may experience significant bone loss, particularly at the hip. In one study of Fosamax, patients who were taking a dose of 6 mg or more of prednisone a day and stopped taking Fosamax lost bone density rapidly. In a three- to four-year follow-up after stopping Fosamax, spine density decreased 5 percent. In contrast, bone density remained stable for those who continued Fosamax. At the neck region of the hip (femoral neck), bone density decreased 9 percent for those who discontinued Fosamax. Those who continued Fosamax had a small loss of less than 1 percent.
HORMONE THERAPY
Since steroids can lead to a decrease in estrogen and testosterone, replacing these hormones has been shown to be beneficial. A few small studies have evaluated hormone therapy in both men and postmenopausal women receiving steroid therapy. Estrogen use in women increases bone density at the spine over 3 percent with no significant change at the hip over one year. Testosterone replacement in men showed similar increases in bone density.
However, because of the increased risk for breast cancer and cardiovascular disease, hormone therapy is no longer recommended as treatment for steroid users. Hormone therapies are usually reserved for improvement in symptoms such as vasomotor symptoms, loss of libido, and loss of potency. Hormone therapy may enhance quality of life and may be given for reasons other than bone protection. Replacing these hormones must be balanced with consideration of the risks of use.
TREATMENT GUIDELINES
In 2010, the American College of Rheumatology updated its guidelines for patients starting or on steroid therapy. For all individuals, basic measures of calcium, vitamin D, and fall prevention are part of the overall treatment. They recommend that management decisions for prescription osteoporosis medicine use be based on assessment of fracture risk and consideration of your age and sex.
This is a synopsis of the recommendations for anyone prescribed prednisone or its equivalent. The recommendations serve as a starting point for evaluating your risk and establishing a management plan that may include prescription medicine for bone protection while taking steroids.
These general recommendations serve as a starting point for helping you and your doctor to individualize your treatment plan based on your risk. A baseline DXA scan is recommended and a scan of the entire spine, called vertebral fracture assessment (VFA), may be considered as well. The identification of silent spine fractures would put you in a higher risk category.
If you are a postmenopausal woman or a man over age fifty, the guidelines recommend using the FRAX calculation to assess fracture risk. Using the ten-year probability of major osteoporotic fracture, three risk groups are identified: low, medium, and high. The “high-risk” group is the same as the National Osteoporosis Foundation classification of 20 percent or higher fracture probability. Therefore, individuals in this group should be considered for therapy even if they are not taking steroids. Those with a fracture probability less than 10 percent are categorized as “low risk,” and those between 10 and 20 percent are categorized as “medium risk.” The guidelines detail specific treatments based on risk category, duration or anticipated duration of use, and dose of steroids. Basically, prescription medicines are recommended for all risk levels and dosages. The exception is “low risk” individuals using less than 7.5 mg a day of prednisone or the equivalent dose of another steroid.
If you are premenopausal or a man younger than age fifty, the guidelines base risk assessment on your history of a fracture not related to trauma along with other risk factors. Recommendations for women in this age group depend on whether they are still interested in starting a family. Lack of research evidence limited the expert panel from making recommendations for some scenarios. Those without a history of fracture are at lower risk, and no recommendations are given for this group.
The guidelines do not address patients using inhaled steroids. However, patients with chronic lung disease who use steroid inhalers are at increased risk for fracture. Measurement of bone density would be appropriate along with evaluation of the overall risk-factor profile.
If you start bone-protective therapy, how long should you continue it? As a general rule, bone-protective therapy should be continued for the duration of steroid therapy. When steroids are stopped, bone density should be reassessed to determine whether further treatment is needed. For example, if you are a postmenopausal woman or a man older than fifty and are at high risk for fracture, you will most likely need to continue osteoporosis therapy to reduce your fracture risk.
The guidelines do not make specific recommendations on monitoring with DXA scans. Since large changes in bone density are possible in the first few months of therapy, bone density changes may be detectable within six months. In general, the standard practice is to recheck DXA after one year of therapy.
CHALLENGES
Other diseases are common if you are taking steroids. Juggling the concerns of “competing” illnesses and treatments can be quite complex and challenging for you and your doctors. Other side effects from steroids, such as difficulty sleeping, high blood pressure, and high blood sugar may receive more attention.
Don't forget about your bones! Dramatic bone losses may happen in a short period of time. Treatment with adequate calcium and vitamin D supplementation and bone-protective medicine, if indicated, can override the harmful bone effects of steroids.
|
The Bare Bones
|