Given the emerging statistics on the prevalence of osteoporosis, this author takes a closer look at key diagnostic techniques and reviews an array of treatment modalities.

Very troubling statistics emerged from the 2004 Surgeon General’s Report on Bone Health and Osteoporosis. It costs $18 billion to care for the 1.5 million bone fractures from osteoporosis that occur each year in the United States. Osteoporosis accounts for 2.6 million trips to a physician’s office, 800,000 trips to the emergency room, 500,000 hospitalizations and results in approximately 180,000 people being placed in nursing homes each year.

Osteoporosis is a skeletal disease in which there is compromised bone strength, resulting in an increased risk of fracture.1 Primary osteoporosis is associated with age-related bone loss and with the menopausal loss of estrogen in women.2 Secondary causes include medications, endocrine conditions, metabolic diseases, gastrointestinal conditions, nutritional deficiencies and other chronic illnesses including rheumatoid arthritis, COPD and type 1 diabetes. Essentially anyone with a chronic illness could have associated secondary osteoporosis.

Studies performed in Canada have shown there is often a combination of primary and secondary causes in patients with osteoporosis. A combination of causes occurs up to 51 percent of the time among men and up to 43 percent of the time among women.3 When I interview patients, I primarily look for medications and endocrine anomalies but I also keep a list of other secondary causes in the back of my mind.

Validated risk factors were consolidated in a fracture risk index that was published in Osteoporosis International in 2001.4 We use this index (see “Fracture Index With BMD” on page 24) on occasion to quantify risk for patients and evaluate their risk for fracture beyond their bone mineral density (BMD).

BMD has been the gold standard over the past decade as a tool for diagnosing osteoporosis and for assessing the risk of future fracture, as well as following patients through the course(s) of treatment. BMD does have some limitations. One cannot measure bone quality via bone mass measurements and clinicians cannot measure all the other components of bone strength.

Bone strength equals bone density plus bone quality. Factors affecting bone quality include microarchitecture, bone turnover, damage accumulation, mineralization and matrix quality.5,6 Microarchitecture refers primarily to the lattice-like look of trabecular bone. This type of bone is more common in the vertebral bodies of the spine. There is a preferential loss of bone in horizontal struts that lead to so-called stress risers. When these stress risers are combined with high bone turnover rates, there is a particularly high potential for fracture. Women have a significant loss of bone at the time of menopause due to the loss of estrogen. Women should pay particular attention to bone health at this time.

Most women do not perceive that osteoporosis is a significant health concern and therefore pay little attention unless they are prompted by their clinicians.7 When you combine breast cancer, myocardial infarction and stroke, it does not come close to the 1.5 million fractures that occur each year as a result of osteoporosis. When you combine this statistic with the fact that only 12 percent of women who have osteoporosis are either evaluated or treated, one can only draw the conclusion that this disease is under-diagnosed and under-treated.8

As clinicians on the front lines, we can provide practical help to those suffering from osteoporosis at a reasonable cost in a reasonable time period despite the constraints of insurance company reimbursement rates.

Can OTC Calcium And Vitamin D Supplements Have A Preventive Impact?
First and foremost, never underestimate the power of simple OTC calcium and Vitamin D. If there is inadequate dietary calcium, the first step is to suggest supplementation. There is significant confusion on this simple issue. While it is beyond the scope of this article to discuss the physiology of calcium or the intricacies of vitamin D, they represent the basic foundation of active treatment.

This was exemplified by a study on the impact of calcium and Vitamin D supplementation among the elderly.9 In the study, the researchers provided calcium supplementation comprised of 500 mg of carbonate and 700 IU of vitamin D3 (cholecalciferol). In regard to non-vertebral fractures in patients 65 years of age and older, the authors of the study found these supplements led to a 50 percent relative risk reduction of these fractures at 36 months.9

For the first time, calcium and Vitamin D became mainstays of non-pharmacologic treatment. Their inclusion became mandatory for all subsequent studies on osteoporosis in phase 2 and phase 3 trials.

However, in regard to supplementation, a Harris consumer study showed that 26 percent of patients take their calcium supplement at the same time or within 30 minutes of taking their bisphosphonates. Even though we spend time teaching our patients how to take bisphosphonates, 23 percent of patients take their bisphosphonates incorrectly.

Vitamin D deficiency is relatively common in the United States. Ordering a vitamin D 25(OH) hydroxyl level is the best indicator to assess vitamin D status. There is now general agreement that a low Vitamin D status is involved in the pathogenesis of osteoporosis. Vitamin D insufficiency can also lead to a disturbed muscle function.10

In elderly people who have lost muscle mass and have little or no exposure to sunlight, this combination can lead to increased fracture risk. Those who are practicing in nursing homes should consider assessing and treating vitamin D deficiency and insufficiency. Insufficiency of Vitamin D is generally between a level of 20 to 30 ng/ml of 25 hydroxy vitamin D. Deficiency would be any level below 20 ng/ml. Vitamin D deficiency leads to poor calcium absorption, secondary hyperparathyroidism and increased bone turnover.11

Vitamin D supplementation can significantly reduce falls and hip fractures.11 Clinicians may prescribe Vitamin D supplements or recommend over-the-counter products. In calcium supplements, vitamin D is included as cholecalciferol, which is more active than ergocalciferol. Multivitamins generally have vitamin D2 or ergocalciferol. This is not as activated as vitamin D3 (cholecalciferol). Prescribed vitamin D is usually calciferol 50,000 units. Patients who have a vitamin D insufficiency or deficiency take this on a weekly basis. Clinicians should recheck vitamin D 25 levels after eight weeks of treatment and adjust to bimonthly or monthly.

What A Meta-Analysis Revealed About Exercise Benefits
Exercise, of course, is also part and parcel of the simple measures one can recommend for both prevention and treatment of osteoporosis.

A patient’s BMD can actually increase as a result of walking. In a meta-analysis of 18 randomized, controlled trials, researchers showed that both the spine and hip showed increased BMD with aerobic exercise, walking and resistance exercise.12 They also found that aerobic exercises improved BMD in the wrist. The meta-analysis also found that the exercises improved muscle strength, tone and balance, and led to a reduction in falls as well.

A Guide To Assessing The Hip And Spine
Falls are responsible for 90 percent of hip fractures.13 Sideway falls are the most common and do have the most serious repercussions for hip fracture.14 For patients who may be at higher risk of these falls, it makes sense to recommend low-tech interventions such as reducing clutter, using night lights, ensuring clear paths to the bathroom, using non-skid backing on bath rugs, etc.

In your decision process whether to treat or not, do not forget you have guidelines to back you up. The National Osteoporosis Foundation (NOF) has recommended that clinicians treat patients with T-scores of -1.5 either in the hip or the spine if they have one or more risk factors or consider treatment when patients have a T-score of -2.0 with no risk factors.

At this point, you are wondering whether to treat the hip or the spine or both. If you happen to have the full radiology report and not just the radiology reading, you will see the evaluation of each individual vertebra, usually L1-L4, as well as total hip and femoral neck T-scores.

Exercise, of course, is part and parcel of the simple measures clinicians can recommend for both the prevention and treatment of osteoporosis. Patients can actually increase their BMD by walking.

When deciding whether to treat these patients, which guideline should you use? The International Society of Clinical Densitometry (ISCD), the professional group that oversees radiology evaluation of these scores, recommends that one should use the lowest reading. If the vertebra cannot be evaluated due to boney exostosis from spondylosis and disc disease, prior compression fracture or another boney lesion, then one should proceed to evaluate the hip. In the hip, the ISCD recommends the use of lowest reading in either the total hip (preferred) femoral neck or the trochanter. If the hip region cannot be evaluated, then assessing the distal radius is recommended.15

A Closer Look At Calcitonin, Hormone Therapy And SERMS
In terms of pharmacologic therapy for osteoporosis, there is anabolic therapy and antiresorptive therapy.
Antiresorptive therapies decrease osteoclastic activity. The mechanism of action of this general category varies between agents. Most of the activities of estrogen and selective estrogen receptor modulators (SERMS) are likely mediated via estrogen receptors (?, beta) and estrogen receptor genes throughout the body. These activities include physiologic and endocrine effects, reduced activity of bone resorbing cytokines, effects on apoptosis and possible nongenomic effects.

The mechanism of action of calcitonin is not completely understood. Calcitonin receptors have been discovered in both osteoclasts and osteoblasts. In vitro studies have shown interruption of the ruffled osteoclast border that is needed to resorb bone.

Hormone therapy with estrogen remains highly controversial. A prospective study showed that employing estrogen alone and progestin in combination facilitates improved BMD and reduces fractures. This was evident in the estrogen only and combination sides of the Women’s Health Initiative. Researchers observed a 38 percent reduction in vertebral fractures among patients who took estrogen only while the combination arm of the study had a 34 percent reduction in vertebral fractures.16

However, another study found that using conjugated equine estrogen alone or in combination led to significant health risks. These risks led to a substantial reduction in the use of hormone therapy and estrogen therapy in postmenopausal women. The Food And Drug Administration (FDA) has recommended the use of these agents for treating climacteric symptoms only, and recommends the use of other agents to prevent osteoporosis.17

Selective estrogen receptor modulators also fall into the category of antiresorptive agents. Evista® (raloxifene) is the agent that is presently available. Researchers have shown that raloxifene has vertebral fracture risk reduction that is sustained over time with a 30 percent risk reduction in vertebral fractures at 60 mg/day at three years and a 36 percent reduction after four years of therapy.18 Hip fracture reduction did not meet statistical significance.

Common side effects include hot flashes and occasionally deep vein thrombosis although this is uncommon unless inactivity occurs or the patient has had a clotting issue in the past. Experimental SERMS are in phase 3 trials and should be available within the next two years.

What You Should Know About Bisphosphonates
Bisphosponates are the largest category of pharmacologic agents available to prevent and treat osteoporosis. Bisphosphonates inhibit bone resorption through osteoclastic uptake. They vary between so-called potency which refers not to the half life in the serum but rather bone and how long they stick to bone. They essentially prevent the osteoclast from burrowing into bone, which starts the coupled process with osteoblasts of bone remodeling. Prevention of this function decreases bone turnover. By facilitating diminished bone turnover, bisphosphonates provide several opportunities for the bone to strengthen. The number of so-called bone mineral units or packets of bone that are remodeling at any one time decrease. This allows for increased time to mineralize the trabecular and cortical bone, which subsequently increases overall bone strength and BMD. Measurements of a patient’s BMD increase the longer the patient is exposed to the drug.19

Researchers have studied bisphosphonates, in particular alendronate and risedronate, up to 10 years and seven years respectively.19 They found that after ten years of alendronate therapy, patients remained free of fractures and had no significant long-term side effects. The same can be said for risedronate.

Alendronate has been shown to reduce the risk of fractures in postmenopausal women with low bone mass due to osteoporosis either with or without existing vertebral fractures.20 Alendronate reduces nonvertebral fractures in women with osteoporosis and the study showed a significant reduction of these fractures by month 24. The authors of the study found that taking alendronate 5 to 10 mg per day for up to four years reduced the risk of nonvertebral fractures by 27 percent and hip fractures by 53 percent.20

Alendronate is also approved for treating glucocorticoid-induced osteoporosis. The research has also shown that alendronate preserves BMD in men and women who require a prolonged course of glucorticoid therapy for a variety of disorders.21

The analysis of risedronate data shows a rapid reduction in vertebral fractures as early as six months after patients begin treatment.22 In the only study in which hip fracture was a primary endpoint, researchers enrolled women between 70 and 79 years of age with femoral neck T-scores below -4 or below -3 with at least one non-skeletal risk factor for hip fracture. They also enrolled women 80 years old or older with at least 1 nonskeletal risk factor for hip fracture or a femoral neck T-score below -4 or -3 plus hip axis length of at least 11.1 cm.

Those who took risedronate for a mean of 2.3 years experienced fewer hip fractures than women taking placebo.23 For women older than 80 years of age, researchers noted no benefit in fracture reduction. The explanation for these observations in the older cohort could have been related to the increasing importance of nonskeletal factors such as the increased risk of falling with age. Researchers did not assess bone mineral density in this group prior to their enrollment in the study and this is a serious limitation to interpretation of the study findings because fracture data from the placebo arm raised the possibility that many of the patients may not have had osteoporosis.

In a separate analysis of data from this study, the researchers did find that risedronate therapy was associated with a reduced risk of both intertrochanteric and femoral neck fractures among older women with osteoporosis.24

Anabolic Therapy: When Is Teriparatide An Appropriate Treatment?
For those patients who have severe osteoporosis as defined by a prior fragility fracture and a low bone density of -2.5 or less, clinicians should consider using teriparatide (PTH 1-34). Teriparatide is the only anabolic therapy that works more on promoting osteoblastic activity, recruiting new cells and reducing apoptosis of differentiated osteoblasts.25,26

Clinical studies indicate teriparatide increases bone quality by increasing bone density, turnover and size.27 Researchers have also noted improvements in microarchitectural elements in both the cancellous and cortical regions.27

When it comes to treating men with idiopathic osteoporosis, researchers have studied the use of teriparatide and found dose dependent increases in BMD at the femoral neck and lumbar spine.28 In this study, the dosing regimens were either 20mcg or 40mcg of teriparatide daily and BMD scores at six, 12, and 18 months showed gains of 4.8 percent, 9.6 percent and 13.5 percent at the lumbar spine respectively.

I should point out that studies using teriparatide in patients who had previously used alendronate showed minimal increases in BMD for the first six months to a year, and then trended towards higher BMDs in the second year of therapy.

The black box warning associated with teriparatide occurred as a result of studies on rats. However, the rat dosage was more than three and up to 60 times the human dosage.29 Teriparatide appears to be quite safe in humans but the FDA has recommended use for only two years. The reason for the recommendation being limited to two years is due to the study on rats. The human studies were stopped on average between 19 to 21 months.

Contraindications of teriparatide include a prior skeletal malignancy, Paget’s disease of the bone, radiation to the skeleton or hyperparathyroidism.

Teriparatide is excellent for the right patient. However, it does have the drawbacks of being a daily injection that requires patient training, and a $600 to $700 cost per month that is quite high compared to other treatments.

Final Notes
Osteoporosis comes down to skeletal health through one’s lifespan. Evaluating risk factors and conducting bone mineral density testing can provide a snapshot of a patient’s future risk of fracture. Low tech interventions include getting enough sunlight, weightbearing exercise and adequate dietary or supplementation with calcium and vitamin D. Pharmacologic options range from SERMS and calcitonin to bisphosphonates and anabolic treatments.

Osteoporosis continues to be underrecognized, under-evaluated and under-treated. Hopefully, as we continue raising awareness of this important public health problem, we can prevent more fractures. By educating patients about proper calcium intake, adequate exercise and sun exposure, we can help increase their ability to keep their bones strong throughout their lives.