Manhattan Physical Medicine and Rehabilitation, LLP


November 19, 2009

Fosamax bad for health of patients and Merck:

A Manhattan federal judge recently rejected Merck & Co's dismissal motion involving 24 cases of more than 900 alleging that its Fosamax drug treatment for osteoporosis caused jaw damage.

The number of cases of osteonecrosis is, of course, growing steadily as more people take the drug for more than 4-5 years, the minimum time at which this type of local bone death occurs with any frequency.

Older Set Gets High and Mighty:

Although younger users actually lose bone strength, cannabis appears to give older people protection, actually retaining bone density, working against osteoporosis. Working with the “knockout” mice that are genetically engineered to lack the relevant DNA, researchers at the University of Edinburgh found that cannabis and cannabis-like compounds had this strangely opposite effect on young versus older mice. There was no evidence about whether the cannabis were preferred more by the younger or the older mice.1

Clinical Pearls before Swine Flu

Never known to prejudicially slight our pharmacological adversaries, this newsletter reports that a relatively unknown journal contains a study suggesting that two bisphosphonates might have action against the avian flu and, yes, the swine flu.2 Avedia and Reclast were cited as promising agents in non-human studies according to this Hong Kong study.

In another communication, Eli Lilly withdrew Arzoxifene from consideration for a wider type of FDA approval because of a mixture of adverse side effects and ineffective treatment against non-vertebral fractures.

Denusomab, new human monoclonal antibody
noted to have few side effects – yet:

It’s a new and clever strategy: instead of the bisphosphonates like Fosamax that slow down the reabsorption of damaged portions of bone, and thereby leave more bone tissue to show up on the DEXA scan, (but not necessarily stronger bones) Amgen is promoting a molecule that attaches to a molecule named RANK, a naturally occurring substance that stimulates that reabsorption. Inhibiting this stimulator appears to work just about as well as the bisphosphonates, maybe better, by essentially the same mechanism: slowing down bone reabsorption by the osteoclast cells. No stomach problems, and no osteonecrosis – at least not yet.

Vertebral fractures in the denusomab group were reduced by 68% beyond the control group in a study of 7,868 women between the ages of 60 and 90 (2.3% for the Denusomab group, compared to 7.2% in the control group).

However, that same molecule, RANKL is also part of the tumor necrosis factor (TNF) that is part of an important anti-cancer surveillance system in the human body. Suppressing it may have consequences of a kind we would not welcome. But we will have to wait a while to find this out.

Dietary

RANK is also achieving stardom status: it appears to be the missing link between obesity and bone loss, a long-standing but previously baffling association, since more weight would ostensibly give bones more stress vis-à-vis gravity. However, Rita Effros and colleagues at UCLA have found that along with raising cholesterol, being overweight appears to generate more free radicals, which in turn stimulate production of more RANK, and thereby promote extracurricular activity on the part of osteoclasts, the bone-eating cells of the body.3

From the Ridiculous to the Subliminal:

Sophocles spoke of flood and famine, saying that ‘for all things, save death itself, mankind has a remedy.’ The great dramatist’s faith emboldens us, but unfortunately, this does not always seem to be warranted. The vertebral fractures that frequently occur with osteoporosis are quite painful. Procedures have been tried over the years to relieve that pain. Splinting, as one might do for a forearm or leg fracture, is not easily applicable in the spine; instead, a form of epoxy very like glue is instilled at the site of the wedge fracture, building it up and strengthening it, and, until now, thought to be effective in reducing the pain.

But recently the New England Journal of Medicine published two independent studies in which, randomized, controlled and double blinded groups were either given the ‘vertebroplasty,’ as it is called, or a sham operation in which the same preparatory talks were given, and the incision was made, but no glue was injected around the vertebral body. Results of both studies confirmed that there was a placebo effect: improved perception of well-being, and reduced perception of pain afterwards, (partially due to the pain-relief medicines routinely given post-operatively) but that all of the advantages really were equal in the sham and operative groups. The glue itself made no difference in the outcome.4

Sophocles to the contrary, better to avoid fractures in the first place. In the case of bones, better to fix it before it gets broken.

So Far So Good

We are now up to 24 people that have done all the preliminaries, had a DEXA scan followed by two reasonably faithful years of yoga, and a second DEXA scan. The results are following the pilot study’s lead. While two people show a little bone loss in the spine, the gains in the hip are just about unanimous. DEXA scans are less reliable in the spine than the hip because arthritis in all the joints of the spine, and calcification of the aorta tend to obscure true differences in spinal bone density. For the 200 plus people doing yoga that we are studying, and the more than 10,000 hours of yoga that they and previously studied patients have done so far, there have been no broken bones, no serious injuries of any kind. No one has needed to see a doctor on account of yoga.

Open Door Policy

The Yoga vs. Osteoporosis study is also open to people without osteoporosis or osteopenia. If an individual’s DEXA scan shows them to be in the normal range, they will need no blood work or lab tests, but rather can receive the DVD simply by sending in the paperwork at “sciatica.org.” In truth, prevention is possibly the best foot that yoga can put forward.

Graph: Bone Mineral Density by Decade

Just looking at what happens over time to the bones without any treatment (medications, yoga, whatever), there is a predictably linear bone loss that appears just after thirty years of age. Couch potatoes, (in red) have less bone at age 30, and will lose enough bone to cross the line into osteopenia by age 45. Normal types (yellow) will not become osteopenic until 65. Those with active exercise histories (red), the prevention group, will be normal until they are 100.


References:

1 Idris AI, Sophocleous A, Landao-Bassonga E, Canals M, Milligan G,David Baker D, van't Hofand RJ, Ralston RH. “Cannabinoid Receptor Type 1 Protects against Age- Related Osteoporosis by Regulating Osteoblast and Adipocyte Differentiation in Marrow Stromal Cells.” Cell Metabolism, Volume 10, Issue 2, 139-147, 6 August 2009 (doi:10.1016/j.cmet.2009.07.006);

2 Qin G, Mao H, Zheng J, Sia SF, Liu Y, Chan L, Lam T, Malik Peiris JS, Lau YL, Tu W. “Phosphoantigen Expanded Human gammadelta T Cells Display Potent Cytotoxicity against Monocyte Derived Macrophages Infected with Human and Avian Influenza Viruses," The Journal of Infections Medicine, August 5, 2009.

3 Graham LS, Parhami F, Tintut Y, Kitchen CM, Demer LL, Effros RB. “Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.” Clin Immunol. 2009 Nov;133(2):265-75.

4 Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, Graves S, Staples MP, Murphy B.”A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures.” N Engl J Med. 2009 Aug 6;361(6):557-68.

Comments, Questions, Criticism, Suggestions?

e-mail: Loren@sciatica.org

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