Your Bones: Role of Bone Turnover Markers

Here's a post from the latest North American Menopause Society's First to Know site. Bruce Ettinger is an osteoporosis expert. See what you think of his comments about this recent article. -- SG

BTMs to predict BMD response

Burnett-Bowie SA, Saag K, Sebba A, et al. Prediction of

changes in bone mineral density in postmenopausal

women treated with once-weekly bisphosphonates. 

J Clin Endocrinol Metab 2009 Jan 13 [Epub ahead of

print] Level of evidence: II-2.

 

Abstract copyright © 2009 The Endocrine Society. All

rights reserved. Used with permission.

 

BACKGROUND: In clinical practice, bone

mineral density (BMD) determined by DXA is

used to monitor response to osteoporosis

therapy. However, 1 to 2 years are usually

required to assess patients’ BMD responses.

The possibility of earlier indicators of a

response or non-response to treatment, such as

changes in bone turnover markers (BTMs), is

of interest to physicians and patients.

METHODS: In this post-hoc analysis of

women treated with once-weekly bis-

phosphonates, we examined the association of

tertile percent change from baseline in BTMs at

3 or 6 months, and association of several

baseline clinical characteristics, with 24-month

percent change from baseline in BMD, and

with percentage of patients showing BMD non-

response (defined as BMD loss at 2 or more of

4 sites) at 24 months. Multivariable analysis

was performed to determine which factors were

associated with BMD non-response.

RESULTS: Patients in the tertile with the

greatest decrease in each of the BTMs had the

greatest mean increase in BMD and the lowest

percentage of BMD nonresponders at 24

months. Several characteristics were

independently associated with BMD non-

response including smaller 3-month reductions from baseline in CTX, bone ALP, and PINP,

younger age of menopause, a family history of

osteoporosis, and higher baseline trochanteric

BMD. Baseline BTMs were not predictive of 24-

month BMD response to therapy. The strongest

associations were for changes in BTMs with

treatment. CONCLUSION: In groups of patients,

short term changes in markers of bone turnover

appear to be predictors of longer term BMD

response and non-response to bisphosphonate

therapy.

 

Comment. It has been over 15 years that BTMs

have been commercially available—yet few

practitioners ever use these tests in management

of osteoporosis. There was high hope that BTMs

would be useful for individual patients in several

ways including: 1) determining fracture risk and

need for treatment; 2) determining what kind of

drug to use; and 3) encouraging adherence and

persistence with therapy. 

 

This report adds to our general skepticism about

application of BTMs to individual patients. Even

using group data (with more power to find

associations), the authors failed to find that

baseline BTM values predicted response to

bisphosphonate (BP) treatment among compliant

users after 2 years. Furthermore, change between

baseline and 3-6 month BTM values showed only

weak associations with 2-year bone density

changes.

 

Typically, studies of BMD in clinical trials of BP

indicate a 90% response rate; in this paper,

alendronate users had an 88% BMD response

rate. Thus, the number of poor responders that

could ideally be found by a perfect BTM test

 

would be about 1 in 10. But, as the current article

shows, BTM tests have poor specificity and

sensitivity when applied to patients starting BPs.

This is not new. Delmas et al,1 using NTx, found

that about one third of patients starting on BP did

not decrease NTx the expected 30%—a lot of

false positives.

 

BTMs have been useful in research, but for

several reasons are not worth the trouble in

practice. First, the cost: in the range of $140 to

$150 per test (double this when getting baseline

and 3-6 month follow-up). Second, the

inconvenience for patients: requiring morning

12-hour fasting blood sampling. Third, the low

predictive value: in this paper, the correlation

coefficient between BTM and BMD was only 

-0.25, meaning that only 6% of the variance in

the BMD increase could be predicted from the

BTM decrease. Finally, investigators who have

examined feedback of BTM results on patients’

drug persistence have found no difference

between giving BTM results and simply

contacting and supporting those patients newly

starting.1

 

It is no wonder that NAMS and other expert

societies have not recommended to clinicians

that they use BTMs to make early treatment

decisions in individual patients.

 

Bruce Ettinger, MD

Clinical Professor of Medicine and Radiology

University of California, San Francisco

San Francisco, CA

Certified NAMS Menopause Practitioner

 

Reference:

Delmas PD, Vrijens B, Eastell R, et al. Effect of

monitoring bone turnover markers on persistence with

risedronate treatment of postmenopausal osteoporosis. 

J Clin Endocrinol 2007;92:1296-1304. 

Build Strong Hips

Another great article from Harvard Women's Health Watch. I'm teaching a workshop next Wednesday on Yoga for Bones & Joints (at the Claremont Resort in Oakland, call 510.549.8512 to register - you don't need to be a member to come), and as you can see I am collating some good data to share at the workshop.

Regarding hips: I find that women especially store emotions in their hips, and that yoga is a great way to release and process it constructively.

Happy hips,

dr. sara gottfried, m.d.

Harvard Women's Health Watch | December 2005

Exercise sampler: Building hip strength

“What weight-bearing exercises do you suggest for strengthening the hipbones?” asks a reader. Here are some suggestions.

One of our greatest fears as we get older is that we will break a hip, an event that can cause permanent disability, depression, and the need for long-term care. Women are twice as likely as men to suffer a hip fracture, partly because we have a greater risk for osteoporosis, a condition that weakens bones.

The chances of developing osteoporosis vary with age, body type, estrogen levels, genetic makeup, ethnicity, lifestyle, level of physical activity, diet, and certain medical conditions. Women are especially vulnerable because they lose bone at an accelerated rate during the first few years after menopause. Along with adequate calcium and vitamin D, exercise is a cornerstone of osteoporosis prevention. It not only helps limit bone loss but also improves balance and coordination and strengthens the muscles we rely on to stay upright. This provides a hedge against falls — one of the main causes of fractures.

Weight-bearing and resistance exercise are especially important. This article highlights some exercises that are particularly good for building hip strength. Keep in mind that they work best as part of an overall program that includes a variety of aerobic, strength, and stretching activities.

Building bone strength

When you put demands on bone, it responds by becoming stronger and denser. Bearing or resisting weight — any activity that works against gravity — stimulates the growth of new bone tissue. Your weight-bearing bones are mainly in your feet and legs and they respond to such activities as walking, jogging, playing soccer, and climbing stairs. Swimming is good for overall fitness, but it isn’t weight-bearing and thus does not improve bone mass or density.

Resistance training, or exercising with weights (see “Working with weights,” below) or resistance bands, can have an even more pronounced effect on bone than weight-bearing exercise. It applies stress to the bones by way of the muscles and tendons. As muscles grow stronger, they pull increasingly harder on bone, which helps build bone mass.

The following exercises work on the muscle groups of the lower body and can help strengthen hipbones.

Working with weights

To perform the exercises illustrated here, you need a sturdy chair with a back and a deep seat; athletic shoes with nonskid soles; an exercise mat (a clean rug or thick towel will do); and hand and ankle weights (for the ankle-weighted exercises, you can use a single ankle weight).

Good free-weight designs include dumbbell-style hand weights with a padded center bar and screw-on end weights and Velcro-closing ankle cuffs with pockets for weight bars.

If you have had hip surgery or have osteoporosis or any other bone or joint condition affecting the feet, ankles, knees, or hips, see your physician or physical therapist before attempting any of these exercises.

How to get the most from working with weights:

To start, take at least 5–10 minutes to get your muscles warm and loose. You can walk (outdoors, indoors, or on a treadmill) or use a rowing machine, stair stepper, NordicTrack, or other piece of indoor exercise equipment.

For best results, do weight training two or three times a week, allowing at least 48 hours for your muscles to recover between workouts. If you have a regular aerobic weight-bearing routine (such as 20–30 minutes of walking or low-impact aerobics), do that first. Follow your resistance training with stretches (such as the hip stretch described here).

Start with a weight you can lift 8 times. (You may need to start with 1 or 2 pounds, or no weight at all.) If you can’t comfortably do 8 repetitions of an exercise, the weight is too heavy. If you can easily do 15 repetitions, it’s too light.

Move only the part of your body that you’re trying to exercise. Don’t rock or sway. Try to keep your hips even.

When lifting a weight, allow three seconds to lift, hold the position for one second, and take another three seconds to lower the weight.

Breathe slowly, inhaling as you lift a weight and exhaling as you lower it. Never hold your breath.

Do one set of 8–15 repetitions (reps), rest for a minute or two, then do a second set. As you gain strength, you may want to add a third set.

When you can perform 2 (or 3) sets of 15 repetitions easily, you’re ready to increase the weight. Add weight until you can lift it only 8 times. Add more weight each time you can easily do 2 or 3 sets of 15 repetitions in a row (don’t forget to rest a minute or two between sets).

Chair stand

Position a chair so that its back rests against a wall. Sit at the front of the chair, with your knees bent and feet flat on the floor, hip-width apart. Lean back in a half-reclining position with your arms crossed and your hands on your shoulders. Keeping your head, neck, and back in a straight line, bring your upper body forward, then stand up slowly. Pause. Slowly sit back down the same way you got up, returning to your original position. Do 8–15 repetitions. Rest, and do a second set. When you’re ready for more: Hold a weight in each hand and cross your hands over your chest.



Front lunge

Stand with your legs hip-width apart. You may want to hold on to a table or counter until you’re sure of your balance. Step forward with your right foot and plant the right heel on the ground. Your right knee should be directly above your right ankle, not in front of it. Roll your back foot forward onto its ball. Keeping your head, neck, back, and hips upright and aligned, lower your body until your right thigh is nearly parallel to the floor (the back knee will be lower). Do not allow the right hip to sink below the level of the right knee. Pause. Push back forcefully to return to the starting position. Alternate legs until you’ve done 8 repetitions on each side. Rest, and do a second set. When you’re ready for more:Hold your arms out to the side or in front of you. Or, try holding hand weights.



Dumbbell squat

Stand with your feet shoulder-width apart. Hold a weight in each hand, with your arms at your sides, palms facing inward. Slowly bend your knees and lower your buttocks 8 inches or more (but do not allow the hips to sink below knee level). Pause. Slowly return to the starting position. Do 8–15 repetitions. Rest. Repeat the set. When you’re ready for more: Increase the weight. You may also try this exercise holding the hand weights at ear level, just above the shoulders.



Hip extension

Wearing an ankle weight, stand 12 inches behind your chair. Holding onto the back of the chair for balance, bend your trunk forward 45 degrees and slowly raise your right leg straight behind you. Lift it as high as possible without bending your knee or pitching forward over the chair. Pause. Slowly lower the leg, returning to the starting position. Do 8–15 repetitions. Repeat with the left leg. Rest, and do a second set.



Side leg raise

Wearing an ankle weight, stand behind your chair with your feet together. Hold on to the back of the chair for balance. With both feet pointed forward, slowly raise your right leg to the side until it is about 8 inches off the floor. Keep your knee straight. Pause. Slowly lower your foot to the floor. Do 8–15 repetitions. Repeat with the left leg. Rest, and do a second set.



Hip flexion

Wearing ankle weights, lie on your back on a mat, with your knees bent and both feet flat on the floor. Rest your hands on your hipbones. Tighten your abdominal muscles and slowly lift your right knee toward your chest until the right foot is about 12 inches off the floor. Slowly lower it. Keep both hips level (it helps to engage your abdominal muscles and press your lower back into the mat). Do 8–15 repetitions. Repeat on the left side. Rest, and do a second set. When you’re ready for more: Do this exercise with a straight leg. With your right knee bent and right foot flat on the floor, extend the left leg so that it is resting on the floor. Keeping the left knee straight, lift the left leg upward until the straight knee is level with the bent knee.



Back extension

Lie facedown on your mat with your knees straight and the tops of your feet against the mat. Place your right arm alongside your body, palm up. Extend your left arm flat on the floor above your head, palm down. Keeping your nose pointed downward, slowly raise your right leg and left arm off the floor (reach out as well as up). Try to keep your head and neck in line with your arm. Pause, and then slowly return to the starting position. Do 8–15 repetitions. Repeat with the left leg and right arm. Rest, and do a second set. When you’re ready for more: Try raising your shoulders and upper chest as you lift your arm and leg.



Hip stretch

You should always stretch after weight-bearing or resistance exercise. Here’s a good stretch for the hips: Lie on your back with your knees bent and feet flat on the floor. Keep your shoulders on the floor at all times. Gently lower both legs to one side, keeping your knees together, and turn your head to the opposite side. You should feel this stretch along the muscles of your hip and side. Hold for 20–30 seconds. Bring your knees back to center, and repeat on the other side.

Get Your Vit D Level Checked

Hi, Friends. We are in the midst of an epidemic of low Vitamin D levels yet the bad news is that conventional physicians rarely check them. Demand your "25-OH-Vitamin-D" level now! Below is a link to a great article from the New England Journal of Medicine from July - a review of the importance of Vitamin D. Basically 50,000 IU per day is too much and the dose that is recommended keeps going up higher and higher. Check your level to see if you're getting enough from sun, food sources and/or supplements.

Here's the link to the article:
http://content.nejm.org/cgi/content/extract/357/3/266