Nutrition Collaboration A collective of health practitioners mentoring one another in topics related to nutrition. Good Afternoon! I want to welcome everyone to the first ever Montana Nutritional Collaboration teleconference! I use the word Collaboration to highlight this gathering together of minds in choosing to support the study of nutrition and how it affect the human frame & psyche.

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. Who? Anyone who wishes to join. You select yourself. When? Second Monday of the month from 1:00 – 2:00pm Why? 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. Rules? To share your knowledge with each other and make sure this knowledge continues to support all people. This information must not be held only for ones self or to serve 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 It is asked that we as a group consider Yogi Bhajan, “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.”

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. What does this mean? At some point we ask you to volunteer to speak on a topic for presentation to the group. This presentation need only be 30-35 minutes in length with a power point or word notes available to the group. You should be able to be present for a Q&A with the group to follow. And the last part of the collaboration, Everyone is encouraged to participate in the Q&A either with a question or to add information. The Q&A should become a roundtable discussion. If you chose not to present, that is your decision and your will not be ousted from the group, you can volunteer a presentation at a later date. If you wish to present a topic to the group in Nov, Dec or Jan (or at a later date) please contact Chelsea at . Lastly I want to thank Joseph Atoll for joining us today and in helping answer questions during the Q&A.

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. We are ready to begin! Please press * now to mute your line if you have not done so already. Without further adieu please welcome: Dr Stephen Dobelbower. He is a Doctor of Chiropractic and a Clinic Nutritionist from Livingston, MT. His presentation today will be on Mitochondrial Biogenesis.

What you’re patients and you need to know 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 Notice is says characterized by. This definition has nothing to do with the causality, but merely what the presence of the disease manifests as

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. Notice is says characterized by. This definition has nothing to do with the causality, but merely what the presence of the disease manifests as

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

Yes No Female Patient Seeks Advice for Prevention of Osteoporosis Is she Caucasian or Asian? Or have Family History of Osteoporosis? Is 12-18 years old or Postmenopausal? Estrogen Deficient or hormonal imbalance? Does her lifestyle put her at risk? Does her diet put her at risk? Is she underweight or underfat? Taking Medication KNOWN to affect bone metabolism or quality? Does she have any health condition that results in a negative calcium balance? Applaud her on achieving high level of health awareness! Yes Discuss genetic history and her responsibility to controllable factors. No Advise Calcium intake of1200mg/day for teenage women and 1200-1500mg/day for menopausal women. Give handout of Calcium Containing foods. Discover real cause of imbalance and correct Discuss natural hormone balancing, HRT risk factors. Discuss lifestyle risk factors: smoking, alcohol, lack of impact exercise. Tailor exercise program. Start smoking cessation program Discuss and assist in good dietary habits to assist in lifelong bone health. Tailor an eating plan to gain appropriate weight/fat. Tailor food supplements to support preventive or corrective needs. Discuss alternative treatment or support options. Give medication handout 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 scanning is by far the most common diagnostic modality in the determination of BMD. This slide gives a bit of info on DEXA Scanning

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. An important point is the determination between cortical bone and trabecular bone. This is the difference between bone quantity and bone quality. i.e Chalk has great density and would look great on DEXA scan, but because of its mineral density with a lack of protein matrix it is very brittle and friable. The last bullet brings up a concern for me. CT scans create substantial radiations dosages, and are linked to cancer genesis. Perhaps MRI or plain film radiography would be less useful, but substantially less carcinogenic.

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 Secondary Osteoporosis is usually a function of underlying endocrine disruption or steroid or other medication.

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? Here’s the standard nutritional approach for Osteoporosis

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 Mitochondrial Biogenesis

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 This drug list includes common medications for GERD, Gastritis, Steroids medications, Diabetes medication, and mood regulators. Highlighted common medication names

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. slgray@u.washington.edu 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, 1.15-1.36) 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,Nzole-D,(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. b.abrahamsen@physician.dk 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. haneye@ohsu.edu 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. sdiem@umn.edu 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. a.grey@auckland.ac.nz 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, placebo-controlled 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