THE PHYSICIAN AND SPORTSMEDICINE - VOL 28 - NO. 3 - MARCH 2000

Osteoporosis Management: What's on the Cutting Edge?

Osteoporosis affects about 10 million Americans, and reports of new ways to diagnose and treat the condition fill the medical literature. Two new developments that show particular promise—ultrasound for bone density assessment and parathyroid hormone (PTH) for treatment—are likely to be highlighted at an upcoming National Institutes of Health consensus conference on osteoporosis.

Both developments are likely to gain a foothold in the primary care setting. (See "Osteoporosis: Understanding Key Risk Factors and Therapeutic Options," February, page 69.) The conference, which will produce a report that will guide osteoporosis management, will be held in late March in Bethesda, Maryland.

Ultrasound: Widespread Screening?

Dual-energy x-ray absorptiometry (DEXA) is still the gold standard in diagnosing osteoporosis and monitoring drug treatment for the condition. However, the number of machines in the United States is inadequate for screening the at-risk population, and DEXA use is often limited by inadequate insurance reimbursement (1).

Ultrasound has been investigated as a lower-cost, portable, radiation-free means of detecting osteoporosis. In 1998, the US Food and Drug Administration approved the first ultrasound device designed specifically for diagnosing osteoporosis. However, according to Clifford J. Rosen, MD, director of the Maine Center for Osteoporosis Research and Education in Bangor, Maine, nearly any ultrasound machine can be used to assess bone density. He expects that this use of the technology will greatly increase the number of women who are screened and treated for osteoporosis. "There are a lot of ultrasound machines out there," he notes.

Researchers (2) recently found that ultrasound, when compared with DEXA, had a low sensitivity (varying between 9% and 47%) but was highly specific (88% to 100%) for predicting bone mineral density categories. Despite the low sensitivity, ultrasound is still a good tool to identify who should undergo a more detailed DEXA evaluation, Rosen says. "If patients are low on ultrasound, they'll be low on DEXA," he says. "It's an efficient screening tool and is reimbursed." Ultrasound, however, should not be used to monitor a patient's response to medication, Rosen says.

Louise Mattson, MD, a family practice physician at Ramsey Health Care for Women in St Paul says physicians at her clinic are making liberal use of ultrasound screening. "With most screening tests, such as mammography, you lose a certain percentage of patients when you ask them to come back or go to another site for the test," she says. In contrast, ultrasound screening takes about 5 minutes in the office, and the patient need only remove a shoe and sock for the test.

Published studies are still clarifying the role of ultrasound in predicting fracture risk. One problem is that researchers aren't sure exactly what bone parameter ultrasound measures. Its interaction with bone is not as well understood as that for radiographs, and research has not established if ultrasound is measuring bone structure, bone quality, or some other physical characteristic (3).

When clinicians interpret ultrasound results, Rosen urges them to use the scoring database provided by the ultrasound machine manufacturer. "For example, a t score of -1 on one company's machine can mean osteopenia, but a t -1 score on another machine may mean osteoporosis," he says. Also, he says, some medical conditions such as arthritis, bone spurs, or fluid retention may skew ultrasound results. One recent study by Tromp et al (4) suggests that correction for the patient's body weight may improve the predictive value of ultrasound measurements.

Rosen expects that the consensus conference will try to establish some guidelines on which patients should undergo ultrasound screening for osteoporosis.

PTH Shows Promise

A recent review (5) of new drugs under development for osteoporosis notes that though current drugs that inhibit bone resorption or stimulate bone formation have improved prevention and treatment for osteoporosis, none has been clearly shown to prevent new fractures once the disease is established. As such, a new class of osteoporosis drugs—known as bone anabolics—is emerging. The most promising bone anabolic is PTH, which has been shown to induce greater bone mass increases than is seen with currently available antiresorptives (6,7).

PTH is known for its role in calcium homeostasis; however, a recent study demonstrated that at least part of the bone-building effects of PTH stems from its ability to inhibit the death of osteoblasts.

"This is a big deal. The increases in bone density are very huge," Rosen notes. He says researchers have noted a 15% to 30% increase in bone mass over 2 years. "Sometimes the bone densities are even coming back into the normal range," he says.

Mattson says she is cautiously optimistic about the new treatment. "PTH will probably have some down side," she says. "Any time you muddle with the endocrine system, you change the whole biologic soup." Rosen says other remaining questions about the new therapy include which patients will benefit most from PTH and whether PTH decreases patients' fracture risk.

The drug is self-administered daily with a subcutaneous injection pen. Each pen contains a 2- to 4-week supply of medication. Of course, injectable therapy may not be feasible for patients who are physically unable to self-administer the drug.

The first PTH-based medication for osteoporosis should reach the marketplace within 3 years, Rosen predicts. He notes that one drug company has already completed a trial, and researchers are investigating PTH as a combination therapy with other osteoporosis drugs.

Lisa Schnirring
Minneapolis

REFERENCES

1. Kulak CA, Bilezikian JP: Bone mass measurement in identification of women at risk for osteoporosis. Int J Fertil Womens Med 1999;44(6):269-278
2. Naganathan V, March L, Hunter D, et al: Quantitative heel ultrasound as a predictor for osteoporosis. Med J Aust 1999;171(6):297-300
3. Sandrick K: Quantitative CT excels at bone mineral analysis. Diagnostic Imaging (serial online). Available at: http://www.dimag.com/db_area/archives/1998/9804whsan.htm. Accessed January 21, 2000
4. Tromp AM, Smit JH, Deeg DJ, et al: Quantitative ultrasound measurements of the tibia and calcaneus in comparison with DXA measurements at various skeletal sites. Osteoporos Int 1999;9(3):230-235
5. Reginster JY, Henrotin Y, Gosset C: Promising new agents in osteoporosis. Drugs R D 1999;1(3):195-201
6. Cosman F, Lindsay R: Is parathyroid hormone a therapeutic option for osteoporosis? a review of the clinical evidence. Calcif Tissue Int 1998;62(6):475-480
7. Dempster DW, Cosman F, Parisien M, et al: Anabolic actions of parathyroid hormone on bone. Endocr Rev 1993;14(6):690-709

Baseball-Funded 'Andro' Study Shows Testosterone Increase

After Mark McGwire's androstenedione use was revealed during the 1998 home run race, Major League Baseball (MLB) responded by promising to fund a study on the supplement. That study, recently published in The Journal of the American Medical Association (1), confirmed previous studies that showed that androstenedione increases serum testosterone concentrations.

Study Details

The study, an open-label, randomized controlled trial, involved 42 healthy men 20 to 40 years old who reported no use of anabolic steroids or related supplements and had not participated in competitive bodybuilding. Subjects received a placebo or 100 mg or 300 mg of androstenedione daily for 7 days. The mean change in serum testosterone was -2% for the placebo group, -4% for the 100-mg group, and +34% for the 300-mg group. Corresponding increases in serum estradiol concentrations were 4%, 42%, and 128%. The authors concluded that the 300-mg daily dose of androstenedione increases serum testosterone and estradiol concentrations in some healthy men.

The JAMA report confirms another recent study of androstenedione that appeared in the European Journal of Applied Physiology (2). The randomized, double-blind, cross-over, placebo-controlled trial involved eight men. The dose used in the study was 200 mg. Prior to these two studies on androstenedione use, the only report in the medical literature that suggested that the supplement raised serum testosterone levels was a 1962 study (3) that involved two female subjects.

The studies validate what physicians and researchers expected, says Gary I. Wadler, MD, associate professor of clinical medicine at New York University School of Medicine in Manhasset, New York. A research question that remains is dose response, he says. "As with supplements in the past, those who use andro are typically using more than the recommended amounts," he says, pointing out that the doses tested in the studies do not reflect the high doses that athletes often take. Wadler is medical adviser to the US Office of National Drug Control Policy.

Will Baseball Change Its Stance?

A statement released by MLB acknowledges the scientific contribution of the study that it funded (along with the MLB Players Association and the National Institutes of Health) and calls for further study to determine if elevated testosterone levels seen in the current study enhance performance.

MLB commissioner Bud Selig told USA Today (4) that the JAMA study will not prompt an immediate ban on androstenedione.

Wadler says even if baseball did ban androstenedione, it would have little effect. "Unless they institute out-of-competition random testing, a ban would just be window dressing," he says.

He calls on MLB and the National Basketball Association, which have resisted this testing, to consider instituting such protocols. "I realize that this is a collective-bargaining issue, but they need to level the playing field," he says. "This is a public health issue." (See "Androstenedione et al: Nonprescription Steroids," November 1998, page 15.)

Wadler notes that the androstenedione issue mirrors a larger problem with such over-the-counter steroids. He says there were at least 343 instances in 1999 in which athletes tested positive for nandrolone, a metabolite of 19-norandrostenedione and 19-norandrostenediol. "Athletes are ingesting a supplement and urinating out a controlled substance," he says.

Lisa Schnirring
Minneapolis

REFERENCES

1. Leder BZ, Longcope C, Catlin DH, et al: Oral androstenedione administration and serum testosterone concentrations in young men. JAMA 2000;283(6):779-782
2. Earnest CP, Olson MA, Broeder CE, et al: In vivo 4-androstene-3,17-dione and 4-androstene-3 beta,17 beta-diol supplementation in young men. Eur J Appl Physiol 2000;81(3):229-232
3. Mahesh VB, Greenblatt RB: The in-vivo conversion of dehydroepiandrosterone and androstenedione to testosterone in the human. Acta Endocrinol 1962;41:400-406
4. Bodley H, Patrick D: No MLB ban on andro this season. USA Today (serial online). Available at http://www.usatoday.com/sports/baseball/mlbfs71.htm. Accessed February 10, 2000

Field Notes

Fitness on the Fly
At the dawn of the new year, trend watchers predicted that fitness centers would spring up at airports and other public facilities. That prediction is holding true in Las Vegas at McCarran International Airport, where 24 Hour Fitness, based in Pleasanton, California, opened the health club chain's first airport-based fitness center.

According to a company press release, the 14,000-sq-ft facility offers a cardiovascular workout area, shower and locker room facilities, a steam room, a dry sauna, and group exercise classes. The fee is $15 for guests who have their own workout gear and $25 for those who need to rent shorts, shirt, socks, shoes, and towel. Other amenities include luggage storage, a kiosk for checking flight information, a pro shop, and to-go health drinks and energy snack bars.

The first airport fitness center was opened in 1998 at the Pittsburgh International Airport by Airport Fitness, Inc.

Father of Athletic Mouth Guard Dies
William D. Heintz, DDS, who developed the modern athletic mouth guard, died at age 91 in Columbus, Ohio, on January 22 after a brief illness.

He was professor emeritus of prosthodontics in the College of Dentistry at The Ohio State University in Columbus. In 1997 he was inducted into the Ohio State Alumni Sports Hall of Fame for his work on the mouth guard and for the 62 years he served as an official at Ohio State home track meets. He was an assistant track coach at the Berlin Olympic Games in 1936—the year Jesse Owens won four gold medals in track and field events—and was a former editorial board member of The Physician and Sportsmedicine.

Exercises That Injure
The President's Council on Physical Fitness and Sports, in the December 1999 issue of its Research Digest, asked a group of exercise scientists from the University of Tennessee, Knoxville, to compile a list of exercises most likely to cause injury when performed incorrectly or by individuals who have poor physical fitness.

The list of culprits includes:

• Yoga plow. While lying supine, the exerciser extends the legs overhead then all the way over the head till the toes touch the floor. The extreme flexion of the neck is inappropriate for people who have arthritis, osteoporosis, or amenorrhea but may not present problems for younger, healthy people.
• Forceful or ballistic neck circles. This exercise may compress neural and vascular structures at the base of the skull and damage disks and other soft-tissue structures. Safe alternative: Perform the exercise slowly with controlled movement in the normal range of motion.
• Bridging. Wrestlers and football players commonly use this exercise to strengthen the neck. While lying supine with knees flexed, the exerciser slowly rises onto the head so that only the feet and head support the body. Bridging places extreme pressure on cervical disks, and as such is inappropriate for almost everyone.
• Fingertip-to-floor and sit-and-reach stretches. Done quickly or repeatedly or performed by people who have tight hamstrings, these positions limit excursion at the hip joint and transfer stress to the connective tissues of the spine. Safer alternative: For the sit-and-reach exercise, extend one leg instead of two. For both exercises, focus on the quality of the movement rather than the distance reached. The spine should make a smooth arc with no flattening or excessive curves.
• Standing quadriceps/hip flexor stretch. Hip abduction during this exercise—which is done with the knee fully flexed and a hand grasping the ankle—stresses the medial structures of the knee. Safer alternative: Use the contralateral hand to hold the ankle.
• Hurdler stretch. Leaning forward to stretch the hamstrings stresses the medial structures of the bent leg. Safer alternative: Bend the knee in front of the body.

Obesity and Depression Risk
Obesity increases the risk of major depression by 37% in women, but in men it decreases the risk by similar proportions, according to a general population study reported in the February issue of the American Journal of Public Health.

Obesity also accounts for differences in suicidal thoughts and attempts. In women, a 10-unit increase in body mass index (BMI) elevated the risk of past-year suicide ideation and attempts by 22%. For men, the same increase in BMI reduced suicidal ideation by 26% and attempts by 55%. Respondents were 40,086 African-American and white participants of the 1992 National Longitudinal Alcohol Epidemiologic Survey.

Conversely, underweight men, when compared with average-weight men, were 81% more likely to have contemplated suicide, 77% more likely to have attempted suicide, and 25% more likely to be clinically depressed. The authors speculated that the variation between the sexes stems from differences in weight and body-build stigmas.