Fosamax, Actonel, Osteoporosis and Toulouse Lautrec
by Jeffrey Dach M.D.
Viewing Osteoporotic Compression Fractures All Day
working as a radiologist for 25 years, a large part of my day was spent
reading X-rays of osteoporotic compression fractures of the spine,
which was quite common. These fractures typically involve the mid
thoracic spine causing loss of height and curvature of the spine, and
Right Image: The modiste Mademoiselle Margouin Year 1900 by Henri Toulouse Lautrec, Musée Toulouse-Lautrec. Image Courtesy of Wikipedia
Vertebroplasty for Compression Fracture - Barbaric?
Working in the hospital over the years, I saw many procedures come and go. A procedure called
vertebroplasty, still in vogue, is used for treatment of compression
fractures. This involves injecting glue into the collapsed vertebral
body under X-Ray control.(1)
Although the procedure may seem somewhat barbaric, it does provide pain
relief and restores some height to the collapsed vertebral body. The
vertebroplasty procedure was invented in
1984 by the French and introduced into the US by Mary Jensen MD. The
procedure is not for the light hearted because during the actual acrylic
glue injection, the acrylic cement may flow into the epidural venous plexus leading to venous thrombosis or pulmonary embolus.(2)
The more refined Kyphoplasty version involves inflation of a balloon
device to expand the collapsed vertebral body just prior to injection of
cement into the cavity. The procedure is quite good at providing some
form of pain relief from the compression fractures.
Prevention Makes More Sense
the surface, it might appear callous for the medical system to wait
years until thousands of women develop severe osteoporosis with
compression fractures, and then intervene with glue injections. Perhaps
some form of prevention would make more sense. The usual preventive
recommendation to take calcium tablets apparently was not effective for
these women presenting with osteoporotic compression fractures. Perhaps
the best preventive plan can be found in Russell Jaffe’s article, Acid-Alkaline Balance and its Effect on Bone Health.(3)
Russell Jaffe MD is a charming and humorous fellow who informed our
small group of docs at his medical seminar that in the old days he ran a
lab at the NIH, and was actually offered the job of Assistant Surgeon
General, but he declined the offer after trying it for a day. He is
also the founder of a supplement company called Perque.(15)
Excess Acid in the American Diet Causes Osteoporosis
to Dr. Jaffe's article, excess acid production from the American diet
causes the chronic calcium loss leading to osteoporosis.(3) The
calcium is pulled away from the bones, and used up as a buffering
agent for the acids which can then be excreted in the urine. The
solution is to alkalinize the diet, and with the help of alkaline food
charts, and pH test strips along with the usual calcium and vitamin
supplements, osteoporosis can be arrested and gradually reversed in a
process which may take years. I would add that a bio-identical hormone
program is also useful for preventing and reversing osteoporosis.
Bisphosphonate Drugs and Toulouse Lautrec's Genetic Bone Defect
the impatient ones who wish to see a prompt increase in bone density,
the FDA approved the bisphosphonate drug Fosamax (alondronate) which was
first introduced in 1995. Merck made 3.2 Billion on 22 million Fosamax
prescriptions in 2006. A major drug study, (FIT) the Fracture Intervention Trial, showed lower fracture rates in the drug group.(4)
And it is true that the bisphosphonate drugs will reward the user with a
prompt increase in bone density. The main question remains
however, how strong is the bone with the increased density? This is an
important question because we know from studies of Toulouse Lautrec that
his increased bone density was not stronger, in fact his bones
were much weaker leading to spontaneous fracture and jaw necrosis. This
is explained below.
Image Above: Henri Toulouse Lautrec courtesy of wikipedia,
short stature from pycnodysostosis.
Genetic Bone Disease Duplicates Action of Fosamax
could fosamax (alondronate) have in common with Toulouse Lautrec, the
famous French Impressionist artist? One day, Toulouse Lautrec's name
came up in conversation, and we puzzled over the cause of Lautrec's
short stature. After looking up the question on the internet, we
discovered that Toulouse Lautrec’s parents were first cousins giving
Toulouse the autosomal recessive genetic disease, pycnodysostosis, which
means dense bones. I had seen X-Rays of this bone disease in text books
while studying for the radiology board exams, but I have never seen it
in actual practice.
Dr. Gelb found Toulouse
Lautrec's dense bone disease was caused by a genetic defect in
cathepsin K, a protease enzyme of the osteoclast cells responsible for
removing and remodeling bone.(5)(6)
Osteoclast cells are bone cells involved in resorption and remodeling
of bone. In this disease, the genetically abnormal bone is very dense on
xrays, and yet looking under microscopic examination, one sees profound
deterioration in trabecular architecture and lamellar arrangement. This
is presumably the reason for spontaneous fracture and jaw necrosis
which occurs in Lautrec's genetic bone disease, and also occurs as an
adverse side effect of the bisphosphonate drugs.(7)
osteoclast dysfunction and resulting bone fragility explains why
Toulouse had spontaneous fractures of both mid femurs at the age of 12
and 14. The mid-femur fractures never healed properly. The non-healing
mid femur fractures caused Toulouse Lautrec to have short stature,
attaining a final height of only four and a half feet.(8)
Image: Spontaneous fracture of mid femur in child with
pycnodysostosis. Courtesy of Taylor et al. J Bone Joint Surg Am 60 (8):
Bisphosphonate Mechanism of Action - Same as Lautrec's Defect
drugs (fosamax and actonel) are taken up by osteoclasts, causing
disruption of osteoclast activity. The osteoclasts are bone cells
involved in bone resorption and remodeling. This loss of the osteoclast
activity inhibits bone resorption and bone remodeling, tasks otherwise
performed by the osteoclasts.(9)
Thus, the bisphosphonate drugs produce a chemical disruption of
osteoclast activity same as the genetic disease of Toulouse
Lautrec. The bisphosphonate drugs also produce the same adverse side
effects, namely jaw necrosis and spontaneous fracture.
Questions About Long Term Safety of Bisphosphonates
conventional medical test for bone density is the DEXA bone scan. And,
indeed DEXA bone scanning does confirm that bisphoshonate drug treatment
increases bone density, and studies such as the FIT (Fracture
Intervention Trial) report drug treatments reduce fracture rates in
severly osteoporotic women over the short term. However, Susan Ott, MD
raises questions about the long term safety of bisphosphonates.(10)
Although the bisphosphonate drugs appear to have short term benefits,
Dr. Susan Ott speculates that over the long term, after 5 years of use,
the drugs cause severe suppression of bone formation, and negative
effects such as microdamage and brittleness.
Reports of Spontaneous Fractures
Jennifer P. Schneider, MD, PhD reports a 59-year old previously healthy woman on long-term alendronate.(11)
While on a subway train in New York City one morning, the train jolted,
and the woman shifted all her weight to one leg, felt a bone snap, and
fell to the floor, suffering a spontaneous mid -femur fracture (see
right image). In the months following, it became clear that the fracture was not uniting.
Image: Spontaneous mid femur fracture courtesy of Jennifer P.
Schneider, MD, PhD January 2006 Volume 61, Number 1 Geriatrics
speculates that increased bone density from the bisphosphonate drug
does not necessarily equate with good bone quality. By decreasing
osteoclast activity and bone resorption, and therefore bone formation as
well, microdamage, and brittle bone may result in fractures.(11)
on a series of 9 patients who suffered spontanous fracture while on
fosamax (alendonate). Five of the nine cases were spontaneous mid femur
Two had bilateral mid femur fractures just like those sustained by
Toulouse Lautrec. Six of the fractures showed delayed or absent fracture
healing. Histomorphometric analysis of the cancellous bone showed
markedly suppressed bone formation, and Odvina raised the possibility that severe suppression of bone turnover could develop during long-term fosamax (alendronate) therapy, resulting in increased susceptibility and delayed healing of fractures.
on 11 patients presenting with necrosis of the jaw, claiming this to be
a new complication of bisphosphonate therapy administration, i.e.
osteonecrosis of jaws.(13)
He advised clinicians to reconsider the merits of the rampant use of
bisphosphonates. Osteonecrosis of the jaw is a common finding in
pycnodysostosis. The bisphosphonates recreate the same clinical profile
of spontaneous mid femur fractures, failure of bone healing and jaw
necrosis which tormented Toulouse Lautrec.
In spite of these widely adverse effects of bisphosphonates, there are four more drugs in clinical trials specifically designed to inhibit cathepsin K, the enzyme defect in Lautrec's genetic bone disease.(14)
FDA approval for use in osteoporosis treatment is expected. Excuse me
here, but perhaps this thinking needs re-evaluation. In essence, these
drugs are creating a population of women with Toulouse Lautrec’s bone
women who sustain fractures while on Fosamax are told by their docs
that the fractures are due to the underlying osteoporosis, not the
drug. For a recent example that I know of, a 60 year old
female sustained a fractured elbow after minor trauma at home in the
kitchen. She claims that, if not for the biphosphate drug, her fracture
would have been much worse. When patients continue to fracture while on
the bisphosphonate drugs, the medical system tends to blame it on the
underlying osteoporosis, not the drug. Sound familiar?
obvious conclusion is that this entire class of bisphosphonate drugs
should be banned, and I predict that they will be banned within the next
few years. Remember that you read it here first. If you would like to
read more about the bisphosphonate drugs, see this article, Bisphosphonates for Osteoporosis, A Closer Look at the Data by Jeffrey Dach MD. (16)
Links to Articles With Related Content:
Fosamax for Pre-Osteoporosis, A Bad Idea .
Fosamax Induced Femur Fractures by Jeffrey Dach MD
Bisphosphonates for Osteoporosis, A Closer Look at the Data by Jeffrey Dach MD
Fosamax, Actonel, Osteoporosis and Toulouse Lautrec by Jeffrey Dach M.D.
Osteoporosis web page on jeffrey dach md Web site
Jeffrey Dach MD
4700 Sheridan Suite T
Hollywood Florida, 33021
References and Links
of Chronic Symptomatic Vertebral Compression Fractures with
Percutaneous Vertebroplasty,Daniel B. Brown Louis A. Gilula Manu Sehgal
Joshua S. Shimony, AJR 2004;182:319–322
and Kyphoplasty, Percutaneous Article Last Updated: Jul 27, 2006
Jeffrey P Kochan, MD, Associate Professor of Radiology and Neurosurgery,
Temple University School of Medicine; Director, Diagnostic and
Interventional Neuroradiology, Department of Radiology, Temple
Balance and Its Effect on Bone Health Susan E. Brown, Ph.D., CCN, and
Russell Jaffe, MD, Ph.D., CCN International Journal of Integrative
Medicine Vol. 2, No. 6 – Nov/Dec 2000
1996 Dec 7;348(9041):1535-41 Randomised trial of effect of alendronate
on risk of fracture in women with existing vertebral fractures. Fracture
Intervention Trial Research Group.Black DM, Cummings SR, Karpf DB,
Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL,
Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE.
J Hum Genet. 1998 April; 62(4): 848–854. Paternal uniparental disomy
for chromosome 1 revealed by molecular analysis of a patient with
B D Gelb, J P Willner, T M Dunn, N B Kardon, A Verloes, J Poncin, and R J Desnick
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA.
- Online Mendelian Inheritance in Man TM #265800 GeneTests,
PYCNODYSOSTOSIS A number sign (#) is used with this entry because
pycnodysostosis can be caused by mutation in the cathepsin K gene (CTSK;
The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 4 1538-1547
CASE SEMINAR Decreased Bone Turnover and Deterioration of Bone
Structure in Two Cases of Pycnodysostosis Nadja Fratzl-Zelman, Angelika
Valenta, Paul Roschger, Alexander Nader, Bruce D. Gelb, Peter Fratzl and
J Bone Joint Surg Am Taylor et al. 60 (8): 1128. Pycnodysostosis. A case report
N Y Acad Sci. 2006 Apr ;1068 :367-401 16831938 (Bisphosphonates: from
bench to bedside. R Graham G Russell The Botnar Research Centre,
Nuffield Department of Orthopaedic Surgery, University of Oxford,
Headington, Oxford, OX3 7LD, UK. The discovery and development of the
bisphosphonates (BPs) as a major class of drugs for the treatment of
bone diseases has been a fascinating journey that is still not over.
The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 3 1897-1899
Long-Term Safety of Bisphosphonates, Susan M. Ott, University of Washington Seattle, Washington 98195
Case Report Jennifer P. Schneider, MD, PhD Should bisphosphonates be continued indefinitely?
January 2006 Volume 61, Number 1 Geriatrics
The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 3 1294-1301
Severely Suppressed Bone Turnover: A Potential Complication of Alendronate Therapy
Clarita V. Odvina, Joseph E. Zerwekh, D. Sudhaker Rao, Naim Maalouf, Frank A. Gottschalk and Charles Y. C. Pak
Int J Oral Maxillofac Surg. 2006 Jul;35(7):588-93. Epub 2006 May 9.
Bisphosphonate-induced avascular osteonecrosis of the jaws: a clinical report of 11 cases.
Dimitrakopoulos I, Magopoulos C, Karakasis D.
Department of Oral and Maxillofacial Surgery, Aristotle University of Thessaloniki, Greece.
Nature Reviews Drug Discovery 5, 785-799 (September 2006) Targeting
proteases: successes, failures and future prospects Boris Turk Cathepsin
K and osteoporosis. Cathepsin K is a lysosomal cysteine cathepsin
predominantly located in osteoclasts and is the major enzyme involved in
bone resorption. The first evidence for this role came from a genetic
study on pycnodysostosis, a rare genetic disorder associated with severe
defects in bone growth, which revealed that an inactivating mutation in
the gene encoding cathepsin K is a causative factor.
Russell Jaffe MD Perque Supplements
Bisphosphonates for Osteoporosis, A Closer Look at the Data by Jeffrey Dach MD
Jeffrey Dach MD
4700 Sheridan Suite T
Hollywood Florida, 33021
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