Transcript Longevity - Park County Chiropractic

Nutrition Collaboration
A collective of health practitioners
mentoring one another in topics related
to nutrition.
Who, When, Why
Anyone who wishes to join –
You select yourself
Second Monday each Month 1 - 2pm
To share and build understanding of
the common and uncommon
knowledge of the practice of nutrition in
the care and treatment of ourselves
and the patients under our care.
Rules
Share your knowledge with each other.
Competition and knowledge hording
only supports lost knowledge. This
group endeavors to share knowledge
and clinical experience to serve not
only ourselves, but all people.
It is asked that we as a group
consider:
“If you want to learn something
read about it. If you want to
understand something, write
about it. If you want to Master
something, teach it.”
Yogi Bhajan
What does this mean?
At some point we ask you to present a topic for
presentation to the group. This presentation
need only be 30-35 minutes in length with a
power point or notes available in Word for the
group. You should be able to do a Q&A with the
group to follow.
Everyone will be encouraged to participate in the
Q&A and it is asked that this become a
roundtable type Q&A.
If you chose not to present, that is your decision
and you will not be ousted from the group.
Please Help This Run Smoothly
 Push * now to mute your line
When the speaker is finished, if you have
a question or wish to add to the
discussion, press * to be put in the queue.
OSTEOPOROSIS
What you’re patients and
you need to know
Stephen Y. Dobelbower, DC DACBN
Doc, I’m worried about
osteoporosis. Can you be of
any help?
Of course, I am an expert
on osteoporosis, both
prevention and treatment.
What is it?
• Book Definition: Osteoporosis is a systemic skeletal disease
characterized by low bone mass and micro architectural
deterioration leading to bone fragility and susceptibility to
fracture
Why does it happen?
• Osteoblasts are cells that build bone
• Osteoclasts are cells that remove or break down bone
When you are young (under age 35) your body’s Osteoblasts
outperform you osteoclasts, leading to both growth in bones
and formation and strengthening of bones.
After age 35 Osteoclasts start to outperform Osteoblasts and
as such we see a gradual weakening or degradation of bone.
Certain lifestyle choices can slow this progressive loss and
prevent Osteoporosis, while other lifestyle choices and
activities can promote the progression of Osteoporosis.
Am I at risk?
• All women 65 or older (longer period of increased osteoclastic activity)
• Postmenopausal women younger than 65 with
additional risk factors
– BMI < 20,
– Smokers, Alcoholics
– Hormone disruption
• On steroids for >3 months/year
• dose equivalent to 5 mg prednisone daily
• Prior fracture with minor trauma
• Vertebral deformity consistent with fracture
• Chronic diseases/drugs associated with bone loss
Female Patient Seeks Advice for
Prevention of Osteoporosis
Is she Caucasian or Asian? Or have
Family History of Osteoporosis?
No
Is 12-18 years old or
Postmenopausal?
Estrogen Deficient or hormonal
imbalance?
Yes
Discuss genetic history and her
responsibility to controllable factors.
Advise Calcium intake
of1200mg/day for teenage women
and 1200-1500mg/day for
menopausal women.
Discuss natural hormone balancing,
HRT risk factors.
Does her lifestyle put her at risk?
Discuss lifestyle risk factors:
smoking, alcohol, lack of impact
exercise.
Does her diet put her at risk?
Is she underweight or underfat?
Discuss and assist in good
dietary habits to assist in
lifelong bone health.
Taking Medication KNOWN to
affect bone metabolism or quality?
Discuss alternative treatment or
support options.
Give handout of
Calcium Containing
foods.
Discover real cause of
imbalance and correct
Tailor exercise program.
Start smoking cessation program
Tailor an eating plan to gain
appropriate weight/fat.
Tailor food supplements to
support preventive or corrective
needs.
Give medication handout
Does she have any health condition
that results in a negative calcium
balance?
Applaud her on achieving high
level of health awareness!
Discuss health conditions; address
other dietary, supplemental support
or lifestyle factors.
Encourage Lifestyle changes
supporting health and
prevention of osteoporosis.
Recheck risk status periodically.
Make any needed changes.
Doc, I am at risk is there any way to
determine how severe it is?
• Physical examination:
– Height loss
• Hyperkyphosis
– Low Body Weight
– Tooth loss
• Strong Vertebral fracture
Indicators
– Wall-occiput distance - any
distance greater than zero is
suggestive of thoracic spine
fracture
– Rib-pelvis distance - 2 finger
breadths or less is suggestive
of lumbar spine fracture
DEXA Scan
•
•
•
•
Most widely used modality for the
clinical measurement of bone
mineral content
Digital imaging to locate the
skeletal regions of interest followed
by estimation of X-ray attenuation
in these regions
Comparison of attenuation at high
and low energy regions of the X-ray
spectra yields an estimate of the
BMD (g/cm2).
DEXA provides bone mineral
density measurements both axially
and peripherally, as well as total
body scans, but is most commonly
applied to scanning of the lumbar
spine (L1-L4) and the proximal
femur.
•
•
•
•
•
•
•
•
•
•
Factors affecting the accuracy of DEXA
measurements:
Variations in soft tissue composition
within the X-ray beam
Correct patient positioning and scan
analysis
Artifacts due to metal or clothing
Scanner calibration
Beam hardening
Interference from Isotopes (Nuc Med
facility in close proximity)
Factors affecting the precision of DEXA
measurements:
Random errors due to photon &
electronic noise
Drifts in scanner calibration
Changes in soft tissue composition
(patient weight gain or loss)
Consistent patient positioning and scan
analysis.
DEXA Scan
•
•
•
Main disadvantage of DEXA is
that it does not enable the
examiner to differentiate
between cortical and trabecular
bone.
Some literature suggest that
DEXA is of limited use in people
with a spinal deformity or those
who have had previous spinal
surgery.
The presence of vertebral
compression fractures or
osteoarthritis may interfere with
the accuracy of the test; in such
instances, CT scans may be more
useful.
Doc, I’ve got my DEXA results, what
do they mean?
• T-score: number of SD
above or below the average
BMD for healthy young
white women
• Z-score: number of SD
above or below the average
BMD for age, ethnicity
and gender -matched
controls
• Normal: T-score greater
than or equal to -1.0
• Low bone mass
(osteopenia): T score
between -1.0 and -2.5
• Osteoporosis: T score less
than or equal to -2.5
• Z-scores lower than -1.5 or
lower than T scores are
suggestive of secondary
osteoporosis
Example
• What’s the
diagnosis?
• What could be
the secondary
cause?
– Is it a disease
– Is it a
medication?
My Doctor recommended the
following. Is this a good idea?
•
Nutrient recommendations
– Calcium 1200-1500 mg/day
– Vitamin D 800-1000 IU/day
• May safely use up to 2000
IU/day
• Aim for level > 30 ng/mL
• Toxicity rare unless chronic
doses > 10,000 IU daily
For deficient vitamin D levels
– 50,000 IU once/twice weekly
for 8-12 doses
– After correction, use 1000
IU/day or 50,000 IU 1-2x/mo
• Of course this is a good idea.
Did she suggest the type of
Calcium you should be
taking?
• Are you aware that some
Calcium sources are less
effective.
• Did she mention the benefits
of vitamin K?
• Did she suggest the need for
protein? Vitamin C? Other
Minerals?
• Did she do any blood testing
to determine your Vitamin D
levels?
My MD has prescribed the
following, what do you think?
FDA-Approved Pharmacologic Options for Osteoporosis
Treatment in Women
Anti-resorptive Agents
• Lower bone turnover, maintain/improve bone mass, stabilize bone
architecture
– Hormone (Salmon calcitonin) (nasal spray or injection)
– SERM (Raloxifene) {Selective Estrogen Receptor Modulator}
– Bisphosphonates
•
•
•
•
Fosamax - Alendronate with/without vitamin D
Actonel - Risedronate
Boniva - Ibandronate
Novartis - Zoledronic acid
Anabolic Agents
• Increase bone turnover with bone formation >bone resorption,
increase bone mass and improve bone architecture
– Forteo - Teriparatide
Osteoporosis Medications
FDA NEWS RELEASE October 13, 2010
• FDA: Possible increased risk of thigh bone fracture with bisphosphonates
The U.S. Food and Drug Administration today warned patients and health
care providers about the possible risk of atypical thigh bone (femoral) fracture in
patients who take bisphosphonates, a class of drugs used to prevent and treat
osteoporosis. A labeling change and Medication Guide will reflect this risk.
Bisphosphonates inhibit the loss of bone mass in people with osteoporosis.
Bisphosphonates have been shown to reduce the rate of osteoporotic fractures -fractures that can result in pain, hospitalization, and surgery-- in people with
osteoporosis. While it is not clear whether bisphosphonates are the cause, atypical
femur fractures, a rare but serious type of thigh bone fracture, have been
predominantly reported in patients taking bisphosphonates. The optimal
duration of bisphosphonates use for osteoporosis is unknown, and the FDA
is highlighting this uncertainty because these fractures may be related
to use of bisphosphonates for longer than five years.
The labeling changes and Medication Guide will affect only those
bisphosphonates approved for osteoporosis, including oral bisphosphonates such as
Fosamax, Fosamax Plus D, Actonel, Actonel with Calcium, Boniva, Atelvia, and
their generic products, as well as injectable bisphosphonates such as Reclast and
Boniva.
Continued on next slide
FDA News Release Continued
"The FDA is continuing to evaluate data about the safety and effectiveness of bisphosphonates when used
long-term for osteoporosis treatment," said RADM Sandra Kweder, M.D., deputy director, Office of
New Drugs in the FDA's Center for Drug Evaluation and Research. "In the interim, it's important for
patients and health care professionals to have all the safety information available when determining
the best course of treatment for osteoporosis."
Today's warning follows a March 10, 2010, Drug Safety Communication announcing the FDA's
ongoing safety review of bisphosphonate use and the occurrence of atypical femur fractures.
The FDA has since reviewed all available data on bisphosphonate use, including data
summarized in the American Society for Bone Mineral Research Task Force report. The
report recommended additional product labeling, better identification and tracking of
patients experiencing these breaks, and more research to determine whether and how these
drugs cause the serious but uncommon fractures.
Based on the FDA's review, the Warnings and Precautions section of all bisphosphonate products for
osteoporosis will be revised, and the FDA will require the inclusion of a Medication Guide to better
inform patients of the possible increased fracture risk.
The FDA recommends that health care professionals be aware of the possible risk in patients
taking bisphosphonates and consider periodic reevaluation of the need for continued
bisphosphonate therapy for patients who have been on bisphosphonates for longer than five
years.
Patients taking bisphosphonates for osteoporosis should not stop using their medication unless told to
do so by their health care professional. Those taking bisphosphonates also should report any new
thigh or groin pain to their health care provider and be evaluated for a possible femur fracture.
Patients and health care professionals should report side effects with the use of bisphosphonates to
the FDA's MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch or by calling
(800) 332-1088.
http://online.wsj.com/article/BT-CO-20101013-710300.html
How did your MD say they would
be assessing your response to
care?
Follow-up BMD in the Treated Patient
• Repeat labs and BMD after two years in patients taking
pharmacotherapy for osteoporosis
• BMD maintained or increased = satisfactory response
• BMD decline
•
•
•
•
Assess technical issues e.g., validity of DEXA comparison
Assess compliance and dosing
Consider and re-evaluate for secondary causes
Patient may be a true “non-responder”
Watts, NB et al. J Clin Densitom. 2004;7:255-261.
Burke, MS. Curr Opin Endocrinol Diabetes. 2004;11:330:337.
How would you feel if you were
medicated for 2 years and found that
it was unsuccessful?
Can you determine treatment
outcomes more quickly?
• YES
• Urinary DPD (Deoxypiridinoline)
– This is a byproduct of osteoclastic activity
(bone resorption/breakdown)
– This can be measured initially with the onset of
treatment, and again at 12 weeks (3 mo’s).
• A decrease suggests a slowing of bone resorption
• No change or increase suggests poor compliance or
failure to respond.
Example
• Here is a before and
after example of a
patient put on
Calcifood Wafers 3BID
for 3 months.
• She had been on
Calcium and Vitamin
D for several years.
• Will she be better in
2007 as a result?
Are you aware that the drug your
taking for _____ could be
causing/speeding your osteoporosis?
Take your pick
The list of medications or substances as possible causes of secondary osteoporosis includes:
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Aluminum-containing antacids – Maalox, Mylanta, Gaviscon, Alu-Cap, Aludrox or
Pepsamar
Proton Pump Inhibitors - Prilosec, Zegerid, Prevacid, Nexium, Zurcal, Somac, Zechin,
AcipHex
Anti-seizure medications
Bisphosphonates - Aclasta, Actonel, Aredia, Boniva, Bonefos, Didronel, Fosamax, Reclast,
Skelid, Zometa
Certain cancer treatments
Cholestyramine - Questran, Questran Light, Cholybar – Due to inhibiting Vitamin K
Hydrocortisone acetate - Colifoam Rectal Foam, Sigmacort, Squibb-HC
Corticosteroids – Cortate, Cortisone, Hysone
Excessive thyroid hormone
Glucocorticoids - when used for long periods, such as over 2 months, can reduce bone mass.
Gonadotropin releasing hormone, Luteinizing-hormone-releasing hormone - used
treatment of endometriosis
Leuprorelin – Viadur, Eligard, Lupron, Lucrin
Thiazolidinedione – Avandia, Avandamet, Avandaryl
Sulfonylureas - Daonil, Semi-Daonil, Euglucon, Glucovance, Glibomet.
Metformin or Glucophage - Glucophage XR, Riomet, Fortamet, Glumetza, Obimet,
Dianben, Diabex, Diaformin.
SSRIs - Celexa, Cipramil, Cipram, Dalsan, Recital, Emocal, Sepram, Seropram, Citox, Cital,
Priligy, Lexapro, Cipralex, Seroplex, Esertia, Prozac, Fontex, Seromex, Seronil, Sarafem,
Ladose, Motivest, Luvox, Fevarin, Faverin, Dumyrox, Favoxil, Movox, Paxil, Seroxat,
Sereupin, Aropax, Deroxat, Divarius, Rexetin, Xetanor, Paroxat, Loxamine, Zoloft, Lustral,
Serlain, Asentra
Smoking
Excessive alcohol
Proton Pump Inhibitors &
Osteoporosis
Proton pump inhibitor use, hip fracture, and change in bone mineral
density in postmenopausal women: results from the Women's Health
Initiative.
Gray SL, LaCroix AZ, Larson J, Robbins J, Cauley JA, Manson JE, Chen Z.
School of Pharmacy, University of Washington, Box 357630, Seattle, WA 98195, USA. [email protected]
Abstract
BACKGROUND: Proton pump inhibitor (PPI) medications have been
inconsistently shown to be associated with osteoporotic fractures. We
examined the association of PPI use with bone outcomes (fracture, bone
mineral density [BMD]).
METHODS: This prospective analysis included 161 806 postmenopausal women
50 to 79 years old, without history of hip fracture, enrolled in the Women's
Health Initiative (WHI) Observational Study and Clinical Trials with a mean
(SD) follow-up of 7.8 (1.6) years. Analyses were conducted for 130 487 women
with complete information. Medication information was taken directly from
drug containers during in-person interviews (baseline, year 3). The main
outcome measures were self-reported fractures (hip [adjudicated], clinical
spine, forearm or wrist, and total fractures) and for a subsample (3
densitometry sites), 3-year change in BMD.
Proton Pump Inhibitors (PPI’s)
RESULTS: During 1 005 126 person-years of follow-up, 1500 hip fractures,
4881 forearm or wrist fractures, 2315 clinical spine fractures, and 21 247
total fractures occurred. The multivariate-adjusted hazard ratios for
current PPI use were 1.00 (95% confidence interval [CI], 0.71-1.40) for
hip fracture, 1.47 (95% CI, 1.18-1.82) for clinical spine fracture, 1.26
(95% CI, 1.05-1.51) for forearm or wrist fracture, and 1.25 (95% CI, 1.151.36) for total fractures. The BMD measurements did not vary between
PPI users and nonusers at baseline. Use of PPI’s was associated with
only a marginal effect on 3-year BMD change at the hip (P = .05) but
not at other sites.
CONCLUSION: Use of PPI’s was not associated with hip fractures
but was modestly associated with clinical spine, forearm or
wrist, and total fractures.
PMID: 20458083 [PubMed - indexed for MEDLINE]
Clinically used proton pump
inhibitors:
• Omeprazole (brand names: Losec, Prilosec, Zegerid, ocid,
Lomac, Omepral, Omez)
• Lansoprazole (brand names: Prevacid, Zoton, Inhibitol,
Levant, Lupizole)
• Dexlansoprazole (brand name: Kapidex, Dexilant)
• Esomeprazole (brand names: Nexium, Esotrex)
• Pantoprazole (brand names: Protonix, Somac, Pantoloc,
Pantozol, Zurcal, Zentro, Pan)
• Rabeprazole (brand names: Zechin, Rabecid,NzoleD,(NEHAL PHARMA Pvt. Ltd.), AcipHex, Pariet, Rabeloc.
Dorafem: combination with
Men, Medications and Osteoporosis
Osteoporos Int. 2009 Apr;20(4):585-97. Epub 2008 Aug 9.
Mapping the prescriptiome to fractures in men--a national analysis of prescription history and
fracture risk.
Abrahamsen B, Brixen K.
Department of Internal Medicine and Endocrinology, Copenhagen University Hospital Gentofte, Copenhagen, Denmark.
[email protected]
Abstract
SUMMARY: A nationwide case-control study was performed in 62,865 men aged 50+ using
fracture data from the national hospital discharge register to screen all redeemed
prescriptions in the past 5 years for significant mapping to fracture risk, employing
measures to control for false discovery rate.
INTRODUCTION: Osteoporosis in men is frequently related to alcohol abuse, hypogonadism,
hypercalciuria, or the use of glucocorticoids. Very limited information is available on the
impact of other medications on fracture risk in men.
METHODS: We conducted a nationwide population-based case-control study collecting
fracture data from the Danish National Hospital Discharge Register and prescriptions from
the National Prescriptions Database (1995-2000). We included men aged 50+ years, with
hospital-treated fractures in the year 2000 (n = 15,716), and age- and sex-matched controls
(n = 47,149).
RESULTS: We identified 3.2 million redemptions of prescriptions for 1,073 different drugs. The
analysis confirmed associations between fracture risk and use of sedatives, anti-epileptics,
anti-psychotics, anxiolytics, SSRI, opioids and other analgesics, loop diuretics, and
glucocorticoids. New associations were also found. We observed an odds ratio (OR [95%
CI] for any fracture) for fracture in users of dopaminergic agents (1.6 [1.3-1.9]) and iron
compounds (1.2 [1.1-1.5]). The largest impact on fracture risk at population level was exerted
by loop diuretics and analgesics.
CONCLUSIONS: An array of drugs is associated with fracture risk in men. The
"prescriptiome" analysis can be used as a surveillance tool for drug-induced osteoporosis
and in the planning of preventive measures.
http://www.springerlink.com/content/5x815102w5960624/fulltext.pdf
SSRIs, Men and Bone Fracture
Arch Intern Med. 2007 Jun 25;167(12):1246-51.
Association of low bone mineral density with selective serotonin reuptake inhibitor use by older
men.
Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, Orwoll E, Bliziotes MM; for the Osteoporotic
Fractures in Men Study Group.
Department of Medicine, Oregon Health & Science University, Mailcode L-475, 3181 SW Sam Jackson
Park Rd, Portland, OR 97239, USA. [email protected]
Abstract
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of
antidepressants that block the serotonin transporter. Osteoblasts and osteocytes express functional
serotonin transporters; serotonin transporter gene disruption in mice results in osteopenia; and SSRI
use has been associated with increased risk of hip fracture.
METHODS: To determine whether SSRI use is associated with lower bone mineral density (BMD) in
older men and to compare the results for SSRIs with those of other antidepressants, we performed a
cross-sectional analysis of data from 5995 men 65 years and older participating in the prospective
cohort Osteoporotic Fractures in Men Study. Main outcome measures included medication use;
BMD at the femoral neck, greater trochanter, and lumbar spine measured by dual-energy x-ray
absorptiometry; and potential covariates.
RESULTS: In adjusted analyses, mean BMD among SSRI users (n=160) was 3.9% lower at
the total hip and 5.9% lower at the lumbar spine compared with BMD in men reporting
no antidepressant use (n=5708 [P=.002 for total hip; P<.001 for lumbar spine]). There
was no significant difference among users of trazodone hydrochloride (n=52) or tricyclic
antidepressants (n=99) compared with nonusers. Adjusting for variables that could be
associated with BMD and/or SSRI use did not significantly alter these results. The
observed difference in BMD for SSRIs is similar to that seen with glucocorticoids.
CONCLUSIONS: In this population of men, BMD was lower among those reporting current
SSRI use, but not among users of other antidepressants. Further research is needed to
confirm this finding in light of widespread SSRI use and potentially important clinical
implications.
PMID: 17592097 [PubMed - indexed for MEDLINE]
Geriatric Women & SSRIs
Arch Intern Med. 2007 Jun 25;167(12):1240-5.
Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic
fractures.
Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, Ensrud KE.
Department of Medicine, University of Minnesota, and Center for Chronic Disease Outcomes Research,
Minneapolis Veterans Affairs Medical Center, 1100 Washington Ave S, Suite 201, Minneapolis, MN
55415, USA. [email protected]
Abstract
BACKGROUND: Serotonin transporters have recently been described in bone, raising the possibility
that medications that block serotonin reuptake could affect bone metabolism.
METHODS: We assessed current use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic
antidepressants (TCAs) and obtained serial bone mineral density (BMD) measurements in a cohort
of 2722 older women (mean age, 78.5 years) participating in the Study of Osteoporotic Fractures, a
prospective cohort study of community-dwelling women. Hip BMD was measured at the sixth
examination and an average of 4.9 years later at the eighth examination. We categorized women as
nonusers (used no SSRIs or TCAs at either examination; n=2406), SSRI users (used SSRIs but no
TCAs at either examination; n=198), or TCA users (used TCAs but no SSRIs at either examination;
n=118). Depressive symptoms were identified using a cutoff score of at least 6 on the Geriatric
Depression Scale.
RESULTS: After adjustment for potential confounders, including the Geriatric Depression
Scale score, mean total hip BMD decreased 0.47% per year in nonusers compared with
0.82% in SSRI users (P<.001) and 0.47% in TCA users (P=.99). Higher rates of bone loss
were also observed at the 2 hip subregions for SSRI users. Results were not substantially
altered when women who scored at least 6 on the Geriatric Depression Scale were
excluded from the analysis.
CONCLUSION: Use of SSRIs but not TCAs is associated with an increased rate of bone
loss at the hip in this cohort of older women.
PMID: 17592096 [PubMed - indexed for MEDLINE]
Diabetes Drug and Bone Formation
•
J Clin Endocrinol Metab. 2007 Apr;92(4):1305-10. Epub 2007 Jan 30.
•
The peroxisome proliferator-activated receptor-gamma agonist
rosiglitazone decreases bone formation and bone mineral density in
healthy postmenopausal women: a randomized, controlled trial.
Grey A, Bolland M, Gamble G, Wattie D, Horne A, Davidson J, Reid IR.
Department of Medicine, University of Auckland, and LabPlus, Auckland City
Hospital, New Zealand. [email protected]
Abstract
CONTEXT: Thiazolidinediones, which are peroxisome proliferator-activated
receptor-gamma agonists, are widely prescribed to patients with disorders
characterized by insulin resistance. Preclinical studies suggest that peroxisome
proliferator-activated receptor-gamma signaling negatively regulates bone
formation and bone density. Human data on the skeletal effects of
thiazolidinediones are currently available only from observational studies.
OBJECTIVE: The objective of the study was to determine whether
rosiglitazone, a thiazolidinedione, inhibits bone formation.
DESIGN: The study was a 14-wk randomized, double-blind, placebocontrolled trial.
SETTING: The study was conducted in the general community.
PATIENTS: Fifty healthy, postmenopausal women participated in the study.
INTERVENTION: Intervention was rosiglitazone 8 mg/d.
MAIN OUTCOME MEASURES: The primary end point was biochemical
markers of bone formation, and secondary end points were a bone resorption
marker and bone mineral density.
•
•
•
•
•
•
•
•
•
•
•
PMID: 17264176 [PubMed - indexed for MEDLINE]Free Article
http://www.ncbi.nlm.nih.gov/pubmed/17264176?dopt=Abstract&holding=npg
Conclusions
•
RESULTS: The osteoblast markers procollagen type I N-terminal propeptide
and osteocalcin declined by 13% (P<0.005 vs. placebo) and 10% (P=0.04 vs.
placebo), respectively, in the rosiglitazone group. These changes were evident
by 4 wk and persisted for the duration of the study. There was no change in the
serum beta-C-terminal telopeptide of type I collagen, a marker of bone
resorption (P=0.9 vs. placebo). Total hip bone density fell in the rosiglitazone
group (mean change from baseline rosiglitazone -1.9%, placebo -0.2%;
between-group difference 1.7%, 95% confidence interval 0.6-2.7, P<0.01);
lumbar spine bone density fell significantly from baseline values in the
rosiglitazone group (P=0.02 vs. baseline) but was not significantly different
between groups (mean change from baseline rosiglitazone -1.2%, placebo 0.2%; between-group difference 1.0%, 95% confidence interval -0.2-2.3,
P=0.13).
•
CONCLUSIONS: Short-term therapy with rosiglitazone (AVANDIA)
exerts detrimental skeletal effects by inhibiting bone formation.
Skeletal end points should be included in future long-term studies of
thiazolidinedione use.
More Diabetes & Bone Formation
•
•
•
•
•
•
•
•
•
J Clin Endocrinol Metab. 2010 Jan;95(1):134-42. Epub 2009 Oct 29.
Effect of rosiglitazone, metformin, and glyburide on bone
biomarkers in patients with type 2 diabetes.
Zinman B, Haffner SM, Herman WH, Holman RR, Lachin JM, Kravitz
BG, Paul G, Jones NP, Aftring RP, Viberti G, Kahn SE; ADOPT Study
Group.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital and
University of Toronto, Ontario, Canada.
Abstract
CONTEXT: An increase in bone fractures has been observed in
women taking thiazolidinediones.
OBJECTIVE: The objective of the study was to examine whether
changes in circulating bone biomarkers provide insight into the
underlying mechanisms responsible for the increase in bone fractures
in female participants randomized to rosiglitazone in A Diabetes
Outcome Progression Trial (ADOPT).
RESEARCH DESIGN AND METHODS: Paired stored baseline and
12-month serum samples were available from 1605 participants (689
women, 916 men) in ADOPT, a long-term clinical trial comparing the
effects of rosiglitazone, glyburide, and metformin on glycemic control
in patients with type 2 diabetes.
PMID: 19875477 [PubMed - indexed for MEDLINE]
Conclusion
•
RESULTS: This subset was well matched to the total ADOPT study
population. In women a marker of osteoclast activity, C-terminal
telopeptide (for type 1 collagen), increased by 6.1% with rosiglitazone
compared with reductions of 1.3% (P = 0.03 vs. rosiglitazone) and 3.3%
(P = 0.002 vs. rosiglitazone) with metformin and glyburide,
respectively. In men, C-terminal telopeptide was unchanged on
rosiglitazone (-1.0%) and fell on metformin (-12.7%; P < 0.001) and
glyburide (-4.3%, P = NS). Markers of osteoblast activity, procollagen
type 1 N-propeptide (P1NP) and bone alkaline phosphatase, were
reduced for women and men in almost all treatment groups, with the
greatest changes in the metformin group (P1NP in females, -14.4%;
P1NP in males, -19.3%), intermediate for rosiglitazone (P1NP in
females, -4.4%; P1NP in males, -14.4%), and smallest for glyburide
(P1NP in males, +0.2%; bone alkaline phosphatase in females, -11.6%).
• CONCLUSIONS: Commonly measured bone biomarkers
suggest that changes in bone resorption may be partly
responsible for the increased risk of fracture in women
taking thiazolidinediones.
Would you be interested in
strategies that may make those
medications unnecessary?
• PPI’s – Gastrex 2TID, Okra Pepsin 2TID,
HiPep, Zypan.
• PPar gamma agonists – Diaplex, Chromium
GTF, gymnema, exercise.
• SSRI’s – MinTran, MinChex, Orchex,
St.JohnsWort IMT, Withania, Nevaton, etc.
Osteoporosis Treatment Strategies
•
•
•
•
•
•
•
•
•
Calcifood Wafers
Cataplex D
Chlorophyll complex perls (vit K)
Cruciferous Complete
Ostrophin PMG
Biost
Cal Ma Plus
Cataplex F
Calcium Lactate
Discussion
• Thanks for your participation