Manhattan Physical Medicine and Rehabilitation, LLP

June 21, 2009

Some things are more easily done than said.

Changes in bone mineral density were followed for 5 years in 300 Mexican Americans in whom the genetic composition was known. The idea was to see which factors influence the bone mineral density apart from genetics. This way, they hoped to uncover the most powerful influences on bone strength over which we, the already born, have some control.

What did they come up with? Age, gender, baseline weight, recent bone loss, and being posmenopausal carried the worst prognosis. But the real question is: Do all these researchers have frowns on their faces? What we want to know is what makes the bones better? How can we affect things positively? After all, there isn’t that much we can do about the genes that determine our gender, nor our age. We can’t do much about menstrual status either. They do not even mention exercise.¹

But that not so bad. The New England Journal of Medicine had one of their rigorously researched articles about world-wide incidence of chronic disease, and did not even mention osteoporosis!² To these scientists 200,000,000 people must not be a big deal.

However, another study suspended the back legs of rats, in order to carefully rule out all the confounding factors, then exercised half of them: The exercised limbs’ bones gained up to 147% in bone volume fraction, +38% in the number of strengthening cross-struts within the bones, and 38% less empty spaces inside them, compared to their other, couch-potato legs.³ Talking genetics again for a moment, those other legs provided just about perfect controls.

Mixed Results

In our zeal for exercise, we have often spoken ill of the medicines used to counter bone loss, particularly the bisphosphonates. However, some positive features have been observed. On April 13 Reuters carried the story of Alexandra Miller’s research finding that Didronel and Boniva, two of these very bisphosphonates, protected mice from radiation, preventing leukemic response to deadly doses in half the mice, and delaying its onset in others.⁴

At the same time, the connection between the bisphosphonates and atrial fibrillation has been affirmed in one study, suggested in two more, denied in one study, and debated in a fifth.⁵

When it comes to breast cancer, the effective two-year drug Teriparatide produces about twice as much as placebo.⁵

Ibandronate does seem a little better than the other bisphosphonates’ generally dismal record regarding stomach upset, bleeding ulcers and other gastrointestinal woes.

Proliferation Treaty?

In a pattern similar to what’s occurring with even more toxic substances, pharmaceutical firms in Holland, India and Japan have begun work on their own bisphosphonates. Several great hopes, such as Denusomab, Zoledronic Acid (Reclast) and tibolone are having their share of problems: Denusomab appears to cause skin infections severe enough to warrant hospitalization, and tibolone seems to increase distant metastases to breast cancer and also increase stroke enough to discontinue a controlled Dutch study 6 months early.^6,7 Tibolone studies were prematurely discontinued in Great Britain also.

Japan is developing minodronic acid hydrate. Dosage has already been set, and in Phase III trials it is superior to placebo in the prevention of fractures. Little is known of its long term adverse side reactions in humans as yet, but it is scheduled for release this year. India’s Bisphosphonate PH-20, however, has been abandoned. The official statement from Halozyme Pharmaceutics asserts they have “decided to deploy resources to [its] other more commercially attractive internal programs in endocrinology, oncology, and dermatology,” but severe ISRs (injection site reactions) were noted.

The major risk with any of these medications may be summed up like this: As you age, you will have more need for the drug, not less. The testing for these medicines does not extend out for as long a time as you’ll be taking them. You will be in uncharted territory. Serious side-effects, such as osteonecrosis, atrial fibrillation, spontaneous fractures (due to a medicine you take to prevent them!) and slower healing are documented after 5-6 years of treatment. Ominously, these were unseen during the initial testing of hundreds of thousands of people. Many of these medicines, once in your bones, never leave. See our earlier newsletters for more on each of these conditions.

If you wish to calculate your risk for fracture, go to FRAX - WHO Fracture Risk Assessment Tool and select your country/ethnicity in the calculation tool menu.

Beware: Exercise is Habit Forming

Albert Einstein was once asked “What is the most powerful force in the universe?” He unhesitatingly responded “Compound interest.” The clinical director of the National Osteoporosis Foundation, Felicia Cosman, M.D., quoting a Tufts University study, asserted that post-menopausal women can gain one to two percent bone density annually through exercise. It is critical to this process that the intensity increases over time. Other recent studies confirm the concept.^8,9 But this is exactly what the progressive yoga poses in our study do.

However, Resistance is not Futile

An Italian study, part of the European Space Agency’s assessment of the perils of outer space, found that absence of resistance to skeletal movement, supplied by gravity but much more strongly by dynamic stretches of the sort one finds in almost every yoga pose, tends to reduce the activity of the cells that destroy bone. Other studies confirm still further that exercise is a powerful anti-inflammatory, releasing PGC1 alpha, which reduces the incidence and severity of rheumatoid and osteoarthritis, Alzheimer’s disease, and a number of types of reproductive and gastrointestinal cancer.

References:

¹ Shaffer JR, Kammerer CM, Bruder JM, Cole SA, Dyer TD, Almasy L, MacCluer JW, Blangero J, Bauer RL, Mitchell BD. “Genetic influences on bone loss in the San Antonio Family Osteoporosis study.” Osteoporos Int. 2008;19:1759-67.

² Anderson GF, Chu E. “Expanding priorities - Confronting chronic disease in countries with low income.” N. Engl.J Med. 2006;356(3):209-211.

³ Lam H, Qin YX: “The effects of frequency-dependent dynamic muscle stimulation on inhibition of trabecular bone loss in a disuse model.” Bone 2008; 43:1093-1100.

⁴ Steenhuysen, Julie, (Reuters) Chicago Sun Apr 19, 2009 3:09pm EDT.

⁵ MacLean C, Suttorp M. “Questioning the Accuracy of a Recent Review of Osteoporosis Medications.” Annals of Internal Medicine. 17 March 2009 | Volume 150 Issue 6 | Pages 424-425.

⁶ Serati M, Uccella S, Bolis P. “Tibolone in older postmenopausal women.” N Engl J Med. 2008 Nov 13;359(20):2173.

⁷ Goodwin PJ. “Tibolone: the risk is too high.” Lancet Oncol. 2009 Feb;10(2):103-4.

⁸ Hamilton CJ, Swan VJ, Jamal SA. “Effects of exercise and physical activity participation on bone mass and geometry in postmenopausal women: a systematic review of pQCT studies.” Osteoporos Int. 2009 Jun 6.

⁹ Silverman NE, Nicklas BJ, Ryan AS. “Addition of aerobic exercise to a weight loss program increases BMD, with an associated reduction in inflammation in overweight postmenopausal women.” Calcif. Tissue Int. 2009 Apr;84(4):257-65. (epub Mar. 11,2009).

¹⁰ The FASEB Journal (http://www.fasebj.org)

Comments, Questions, Criticism, Suggestions?

e-mail: Loren@sciatica.org

or write to:
Allen N. Wilkins, M.D.
1009 Park Avenue
New York, NY 10028