Know Bones About It Lynn Chadd - Amazon S3...Building and maintaining strong bones is essential for an active and contented life! • Bone health is a major concern for menopausal

Know Bones About It: Addressing Bone Health for the Long Term

Lynn Chadd, MSN, ARNP

Building and maintaining strong bones is essential for an active and contented life!

• Bone health is a major concern for menopausal women. Osteoporosis and osteopenia are common diseases of bone weakness, and these often progress without symptoms or pain. In fact, most often the first sign a patient will have of bone weakness is a broken bone.

• According to the National Osteoporosis Foundation:• 80% of the estimated 10 million Americans with osteoporosis are women

• Approximately 1 in 2 women over age 50 will break a bone because of osteoporosis

• A woman’s risk of breaking a hip is equal to her combined risk of breast, uterine and ovarian cancer

National Osteoporosis Foundation www.nof.org (Accessibility verified 12/1/14)

Bone Remodeling

• The breakdown of old bone and building of new bone • Lifelong process where mature bone tissue is removed from the skeleton (aka bone resorption) and new bone tissue is formed (aka ossification).

• These processes control the replacement of bone following injuries like fractures, but also rebuild the normal wear and tear on bones due to daily activities.

Hadjidakis DJ, Androulakis II. Bone Remodeling. Ann N Y Acad Sci. 2006 Dec;1092:385‐96.

Bone Remodeling

• Osteoclast cells continually travel through bone tissue looking for older bone in need of renewal. They dissolve (resorb) the old bone, leaving tiny, unfilled spaces behind.

• Osteoblasts then move into these spaces and produce new bone

• At any stage in life, our bone status is a product of the balance between these two functions of bone resorption and new bone formation.

Lee, John MD. What Your Doctor May Not Tell You About Menopause. New York: Warner Wellness, 1996. Print.

Bone Remodeling• Bone remodeling is a continuous activity throughout life, requiring a balance between breakdown and building to maintain healthy bones.

• In the first year of life, almost 100% of the skeleton is replaced

• In adults, remodeling proceeds at about 10% per year.

Bone Health and Osteoporosis: A Report of the Surgeon General. http://www.ncbi.nlm.nih.gov/books/NBK45504/. Accessibility verified 12/8/14.

Bone Loss

• When the rate of breakdown exceeds the rate of building, it results in a net loss of bone and thus, a decrease in bone mass (osteopenia/osteoporosis).

• Peak bone mass is reached around age 30 for most people, after which time, it steadily declines.


Clinical Features

• Back pain, caused by a fractured or collapsed vertebra• Loss of height over time• A stooped posture• A bone fracture that occurs more easily than expected• Osteoporotic fractures usually occur in skeletal sites that are rich in trabecular bone. The most common low‐energy fractures are those of the vertebrae, wrist and hip


Osteoporosis

• “Porous bone”• Osteoporosis is defined by the World Health Organization as a bone mineral density of 2.5 standard deviations or more below the mean peak bone mass (average of young, healthy adults) as measured by dual‐energy X‐ray absorptiometry (DEXA).

• Bone loss is the result of osteoclast dominance.• 54 million Americans have osteoporosis. • Studies suggest that one in two women and up to one in four men will break a bone due to osteoporosis.

• 20% of the women who fracture their hip die within a year


Osteopenia

• Osteopenia refers to bone density that is lower than normal peak density, but is not low enough to be classified as osteoporosis.

• Osteopenia puts patients at greater risk for developing osteoporosis.


Most Common Fractures

• Spinal vertebrae • Vertebral compression fractures are the most common fractures seen with osteoporosis, occurring in approximately 700,000 patients each year.

• Hip • most costly and debilitating• In 1991, Medicare costs for hip fractures were estimated to be $2.9 billion

• 1 in 5 hip fracture patients die within a year of their injury.• Distal forearm (wrist)• Proximal humerus (shoulder)• Ribs

American Academy of Orthopaedic Surgeons. http://orthoinfo.aaos.org/. Accessibility verified 12/3/14.Centers for Disease Control and Prevention. http://www.cdc.gov/HomeandRecreationalSafety/Falls/adulthipfx.html. Accessibility verified 12/3/14.

Bone loss: Risk Factors

• Family history of osteoporosis• Previous fractures• White race• Poor nutrition• Alcoholism or smoking history• Low weight and BMI• Early menopause (before age 45)• Parity• Physical inactivity• Rheumatoid arthritis• Gastrointestinal disorders/gastric bypass• Corticosteroid use

American Academy of Family Physicians www.aafp.orgAccessibility verified 12/2/14.

Unchangeable Risks

• Sex: Women are much more likely to develop osteoporosis than are men.

• Age: The older you get, the greater your risk of osteoporosis.• Race: greatest risk of osteoporosis in Caucasians, Hispanic and Asian population.

• African Americans: lowest risk, 53% of women, 24% of men.• Caucasians: 77% of Caucasian women, 43% of Caucasian men• Hispanic Americans: 86% of women, 53% men

• Family history: Having a parent or sibling with osteoporosis puts you at greater risk, especially if you also have a family history of hip fractures.

• Frame size: Men and women who have small body frames tend to have a higher risk because they may have less bone mass to draw from as they age.

Burge R, Dawson‐Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis‐related fractures in the United States, 2005‐2025. J Bone Miner Res. 2007 Mar;22(3):465‐75. PMID: 17144789

Changeable Risks• Diet:

• Consume foods that contain calcium/vitamin D• Caffeine can decrease calcium absorption• Soda can contribute to bone loss. Likely via caffeine and phosphorus. • High protein diets may cause the body to excrete calcium

• In ♀ w/osteoporosis, raising daily protein intake from 47 to 142 grams/day doubled amount of calcium lost in urine.

• Smoking: smokers may absorb less calcium from their diets. • Alcohol consumption: Drinking heavily can lead to bone loss. Limit alcohol to no more than 2‐3 drinks per day.

• Weight: Women who are thin are at greater risk for osteoporosis• Physical activity: ‐Weight bearing exercise helps to build bones and keep them strong.

• Medications ‐Many medications, glucocorticoids in particular, affect bone mass.

National Osteoporosis Foundation. www.nof.org. Accessibility verified 12/3/14.National Institutes of Health: Senior Health. http://nihseniorhealth.gov/. Accessibility verified 12/3/14.Cooper C et al. Dietary protein intake and bone mass in women. Calcif Tissue Int. 1996 May;58(5):320‐5.Fulgoni VL 3rd. Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003‐2004. Am J Clin Nutr.2008 May;87(5):1554S‐1557S

Medications Associated with Bone Loss Acceleration

• Prednisone• PPI’s• Bisphosphonates?• SSRI’s• Anti‐psychotics• Aromatase inhibitors – breast and prostate CA tx• Anti‐convulsants• Heparin / warfarin • Thiazolidinediones ‐ diabetes• Transplant medications• GnRH agonists – for breast and prostate CA tx• Excess thyroid hormone• DMPA (depo medroxyprogesterone acetate) – contraceptive

https://www.accp.com/docs/bookstore/psap/p7b03.sample04.pdf

Fracture Risks Associated with Aromatase Inhibitors

• Anastrazole / Letrazole rate of bone loss approximately 4‐6% over 5 years.

• Fracture risk for Anastrazole 11% after 5 years• Fracture risk for Letrazole 8.6% after 5 years• Fracture risk for Tamoxifen is 3.3% after 5 years (Randomized controlled clinical trials.)

• Translates to one excess fracture for every 35 women treated with AI over five years.

https://www.accp.com/docs/bookstore/psap/p7b03.sample04.pdf

Antidepressants and Bone Loss

• Among 6,645 subjects, 192 (2.9 %) were using SSRIs or/and SNRIs at baseline. During the 10‐year study period, 978 (14.7 %) participants experienced at least one fragility fracture.

• SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95 % confidence intervals (CI), 1.48‐2.39).

• “Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.”

Osteoporosis Int. 2014 May;25(5):1473‐81. doi: 10.1007/s00198‐014‐2649‐x. Epub 2014 Feb 25.

Proton Pump Inhibitors and Bone Loss

• PPI’s interfere with mineral absorption.• PPI’s decrease HCl production• PPI’s increase gastrin production – increased gastrin levels may cause histamine production through hypertrophy of gastric enterochromaffin like cells, which could lead to bone loss.

• Proton pumps have been identified on osteoclasts, and may be used for the excretion of hydrogen ions for bone resorption.

• PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip.

Bone. 2013 Nov;57(1):269‐71. doi: 10.1016/j.bone.2013.08.013Am J Gastroenterol. 2012 Sep;107(9):1361‐9. doi:10.1038/ajg.2012.200. Epub 2012 Jul 10.

Glucocorticoids and osteoporosis

• Glucocorticoid administration is the most common cause of secondary osteoporosis

• Several large case‐controlled studies show clear and strong associations between glucocorticoid exposure and fracture. Arth Rheum. 2003;48:3224–3229.

• An increase in vertebral and hip fractures occurs with as little as 2.5 to 7.5 mg/day of prednisolone (equivalent to 3.1 to 9.3 mg of prednisone).

• In a cohort study of patients aged 18 to 64 years receiving glucocorticoids for a variety of disorders, the combination of higher dose, longer duration and continuous use had the greatest effect on the incidence of fractures Endocrinol Metab Clin North Am. 2012 Sep;41(3):595‐611.

Contraceptives May Accelerate Bone Loss

• Depo‐Provera (medroxyprogesterone) is the most widely used contraceptive worldwide

• DMPA use clearly associated with loss of BMD• 2004 FDA added black box warning to DMPA• Large % Mirena (progestogen ‐‐levonogestrel) users annovulatory

IsleyMM, Kaunitz AM. Update on hormonal contraception and bone density. Rev EndocrMetab Disord. 2011 Jun;12(2):93‐106Seifert‐Klauss V, SchmidmayrM, Hobmaier E, et al. Progesterone and bone: a closer link than previously realized. Climacteric. 2012 Apr;15 Suppl 1:26‐31.BahamondesMV, Monteiro I, Castro S, et al. Hum Reprod. 2010 May;25(5):1158‐64.Prospective study of the forearm bone mineral density of long‐term users of the levonorgestrel‐releasing intrauterine system.Miller PD. Unrecognized and unappreciated secondary causes of osteoporosis. EndocrinolMetab Clin North Am. 2012

How is osteoporosis related to menopause?

• While there are multiple factors leading to osteoporosis, hormones play a significant role.

• Osteoporosis begins anywhere from 5 to 20 years prior to menopause when hormone levels are still high. Osteoporosis accelerates at menopause.

• Estrogen regulates the activity of osteoclasts• Progesterone and testosterone regulate the activity of osteoblasts, which affect the formation of new bone.

Mead J; Lommen E. Slim, Sane & Sexy: Pocket Guide to Natural, Bioidentical Hormone Balancing. Oregon City, OR:CalarogaPublishing,2008. Print.

Testing: DEXA

• Guidelines from multiple organizations, including the American College of Obstetrics and Gynecology, the US Preventive Services Task Force, and the National Osteoporosis Foundation recommend beginning DEXA screening for osteoporosis at age 65 in women and men at age 70 with no risk factors.

• Medicare will pay for a bone scan every two years in women with osteoporosis or who are at high risk.

• Retest sooner if taking high dose steroids (mb every 6 months)

• Women with normal bone scans can wait longer

American Academy of Family Physicians www.aafp.orgAccessibility verified 12/2/14.National Institutes of Health: Medline Plus. http://www.nlm.nih.gov/medlineplus/ency/article/007197.htm. Accessibility verified 12/2/14.

DEXA Results

• Results reported as T‐scores and Z‐scores• T‐score compares your bone density with that of healthy young women

• Z‐score compares your bone density with that of other people of your age, gender and race.

• With either score, a negative number means you have thinner bones than average. The more negative the number, the higher your risk of bone fracture.

Mayo Clinic. www.mayoclinic.org/tests‐procedures/bone‐density‐test/basics. Accessibility verified 12/2/14.

T‐score

• A T‐score is within the normal range if it is ‐1.0 or above• Between ‐1 and ‐2.5: osteopenia• Below ‐2.5: osteoporosis• Treatment recommendations depend on total fracture risk. This risk can be calculated using the FRAX score.


Z‐score

• The z‐score is the number of standard deviations above or below what’s normally expected for someone of the patient’s age, sex, weight, and ethnic or racial origin.

• Z‐score is ‐2 or lower: something other than aging is causing abnormal bone loss.


WHO Fracture Risk Assessment Tool

http://www.shef.ac.uk/FRAX/tool.jsp

DPD ‐ Deoxypyridinoline

• Bone is composed mostly of bone matrix which contains both organic and inorganic components.

• The inorganic portion is bone mineral and the organic portion is primarily Type I collagen.

• Collagen is linked together by molecules known as pyridinium cross‐links.

• When collagen is broken down (as occurs in bone resorption), these cross links are excreted in urine with additional breakdown products attached, including deoxypyridinoline (DPD).

DPD

• While measuring bone mineral density remains the standard for diagnosing osteoporosis/osteopenia, monitoring urinary deoxypyridinoline (DPD) levels offers insight into the rate of resorption.

• Results greater than 7.4 for women and 5.4 for men indicate a rate of bone loss exceeding that which occurs in a healthy, young population

• Elevated results likely warrant treatment

When to Test DPD

• DPD can be a useful tool to: • Identify the rate of bone loss• Improve assessment of an individual’s fracture risk• Monitor treatment of osteoporotic/osteopenic patients

• Decreasing DPD levels indicate a response to therapy

• Once an initial DPD level has been measured, it is recommended to retest 3 months after initiation of therapy with annual monitoring after levels reach normal range.

• If levels remain elevated after initiation of therapy, investigation of compliance, dose response and additional physiologic processes may be warranted.

DPD Kit & Collection Details

• Turn around time of 5 Days• DPD will have a separate kit. Patient can mail their collection back in the DPD kit box if testing alone, or include in the hormone kit box if paired with H testing (or NT/H.)

• Patients will collect their sample before 10 am. First or second void of the day

• DPD testing can be run from an NT tube, but NT’s CANNOT be run off a DPD tube.

• Prior to sample collection, patients can eat and drink normally.• Patients are encouraged to ship the sample back on the same day of collection, or they should freeze the sample until ready to ship.

• Requisition form and instructions are included on the same piece of paper

DPD Report

These things can cause DPD levels to decrease (GOOD)

• Potassium• Magnesium• Beta‐carotene• Vitamin D• Fiber intake• Calcium supplementation• Physical activity• Hormone therapy

These things can cause DPD levels to increase (BAD)

• Bed rest• Running• Alcoholism• Pregnancy• Hyperparathyroidism• Hyperthyroidism• Osteomalacia

• Some cancers• Osteoporosis/osteopenia• Paget disease• Kidney failure• Diets low in copper• Corticosteroid use• Fractures – up to 1 year post fracture

Other Pertinent Labs

• Hormones• Vitamin D• Thyroid• Lipids: elevated lipids associated with increased bone loss

Parhami F, et al. Role of lipids in osteoporosis. Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2346‐8.

Osteoporosis TreatmentsConventional

• Bisphosphonates• Fosamax, Boniva, Actonel (oral)• Reclast, Aclasta (IV)

• For prevention of fractures three Cochrane reviews of biphosphonates came to the conclusion that there was no significant reduction in hip fracture for primary prevention and a small but statistically significant reduction in hip fracture for secondary prevention

• New bone formation 100x lower in women taking Fosamax, result: fragility fractures during normal daily activities

• Odvina CV. Severely suppressed bone turnover; a potential complication of alendronate therapy. J Clin Endocrinol MetabMar;990(3):1294‐301.

Adverse Effects of Bisphosphonates

• Stomach and esophageal erosions• Esophageal cancers "Oral bisphosphonates and risk of cancer of esophagus, stomach, and colorectum: case‐control analysis within a UK primary care cohort". BMJ. 2010 Sep 1;341:c4444. doi: 10.1136/bmj.c4444

• With bisphosphonate use, there is an increased fracture risk due to over suppression of bone turnover (unusual fractures, ie femur).

• Subtrochanteric/femoral shaft fractures, unlike intertrochanteric/femoral neck fractures, are positively associated with higher adherence to long‐term (≥3 years) oral bisphosphonates in the elderly female Medicare population.

• Osteoporos Int. 2014 May 21.

• As of May 16, 2014, 1512 papers in PubMed.gov re: bisphosphonates and osteonecrosis of the jaw

• Bisphosphonates and their related effects on the jaw have been established since 2001.

• The pathogenesis of bisphosphonaterelated osteonecrosis of the jaw (BRONJ) is multifactorial and still under investigation.

More Conventional Treatments…

• Denosumab: prevents normal bone remodeling by binding to RANKL

• Forteo (teriparatide): fragment of human parathyroid hormone

Patent osteoporosis meds are notthe best long term solution.

• Bone is constantly remodeling throughout our lives• It makes no sense to take a patent medicine that, in the case of BPs and denosumab, at best, only prevents the removal of old, worn‐out bone

• Increases fracture risk in as little as 4 months (BPs, denosumab)

• Is highly likely to cause fracture within 3 years (BPs, denosumab)

• Has numerous other serious adverse side effects –including Afib (BPs, denosumab), immune suppression (denosumab), osteosarcoma, chronic cortisol elevation (teriparatide)

Ellis, Wendy ND. Clinical features in the prevention, diagnosis and treatment of osteoporosis. Presented at the Women In BalanceConference, National College of Natural Medicine. June, 2014.

Nutrients Critical to Bone HealthVitamins

• D: up to 10,000 IU daily • K2: 100 mcg/d if MK‐7, 15 mg/tid if MK‐4• B6: 50mg • B12: 500mcg• Riboflavin: 25mg • Folate: 1,000‐2,000mcg • C: 1,000‐2,000mg • E: 400IU mixed tocopherols• Omega 3 fatty acids: 1,000mg

Ma J et al. Americans are not meeting current calcium recommendations. Am J Clin Nutr. 2007 May;85(5):1361‐6.Ellis, Wendy ND. Clinical features in the prevention, diagnosis and treatment of osteoporosis. Presented at the Women In Balance Conference, National College of Natural Medicine. June, 2014.

Nutrients Critical to Bone HealthMinerals• Calcium

• NIH RDAs for Ca• Age 19‐50: 1000mg• Age 51‐70: 1200mg females; 1000mg males • Age >70: 1200mg females and males

• Magnesium: 250mg bid• Boron: 3mg • Zinc picolinate: 15mg • Copper: 1‐2mg • Manganese: 5mg • Molybdenum: 50mcg • Silicon: 10mg • Selenium: 50mcg • Strontium citrate: 680mg/d until initial improvement, then 200‐400mg/d

Ma J et al. Americans are not meeting current calcium recommendations. Am J Clin Nutr. 2007 May;85(5):1361‐6.Ellis, Wendy ND. Clinical features in the prevention, diagnosis and treatment of osteoporosis. Presented at the Women In Balance Conference, National College of Natural Medicine. June, 2014.

Balance Hormones

• Test and treat any identified imbalances in estradiol, progesterone, testosterone, DHEA, and cortisol levels.

Clinical Pearls

• Not all DEXA scanners are created equal. There are slight differences in the calibration of different manufacturer’s machines. Ideally patients should get all of their bone scans on the same DEXA scanner. Getting retested on a different scanner could give a false impression of bone loss or gain.

• Strontium use can interfere with DEXA results, giving a false increase in BMD scores

Case Study Over Time….

• Osteopenia• Menopausal Symptoms• Hypoadrenia• Sleep disturbance

• Clinical pearl….be patient!

PB‐56 year old femaleSymptoms/History 2005

• PB came in to discuss options for hormone balancing

• Post menopausal bleeding—related to poor hormone balance

• Hot flashes• Night sweats• Poor sleep• Vaginal dryness• Painful intercourse• Osteopenia

PB‐Test results: DEXA 4/28/2003

PB 56 year old femaleComprehensive hormone panel results‐2005

PB 56 years oldTreatment

• Adjust hormones• DC Biest capsule and change to Biest 0.5 mg, topically, twice daily.

• Continue Progesterone 30 mg topically, twice daily.• Add Testosterone 0.25 mg/DHEA 2.5 mg, topically, twice daily.

• Iodoral 12.5 mg—one tablet daily• Calcium Citrate 500 mg once daily• Magnesium 500 mg once daily• Vitamin D3 5000 IU once daily• No caffeine• Increase weight bearing exercise

PB‐62 year old femaleTest results: DEXA 10/4/2009, 2010, and 2011

(PB‐62 years old)Test results: DEXA 10/4/2011

(PB 64 years old) Test Results: DEXA 10/4/2011

(PB 64 years old) Test Results:Basic hormone panel 12/2012

PB 64 years old: Vitamin D3 levels 12/2012

(PB‐65 years old)Test results: DEXA 11/27/2013

Summary

• The trick to treating bone loss is to be patient, grasshopper!

• Bones changes happen slowly over time.• Nutrition and regular activity play a significant role in building and maintaining bone mass.

Documents

Know Bones About It Lynn Chadd - Amazon S3...Building and maintaining strong bones is essential for an active and contented life! • Bone health is a major concern for menopausal