Osteoporosis DeAnn Cummings, MD January 12, 2012

OsteoporosisOsteoporosis

DeAnn Cummings, MDDeAnn Cummings, MD

January 12, 2012January 12, 2012

Why Does it Matter?Why Does it Matter?

44 million people in U.S. with low bone mass44 million people in U.S. with low bone mass 2 million osteoporotic fractures per year2 million osteoporotic fractures per year $17 billion spent per year on osteoporotic fractures $17 billion spent per year on osteoporotic fractures

and their complicationsand their complications 20% increased mortality over 5 years following a 20% increased mortality over 5 years following a

vertebral fracturevertebral fracture 10-30% increased mortality over one year following a 10-30% increased mortality over one year following a

hip fracturehip fracture 17% for women17% for women 30% for men30% for men

Why Does it Matter?Why Does it Matter?

50% require nursing home care after hip 50% require nursing home care after hip fracturefracture

30% need assistance with daily activities30% need assistance with daily activities Only 20% return to previous level of Only 20% return to previous level of

functioningfunctioning

DefinitionDefinition

A microarchitectural deterioration of bone A microarchitectural deterioration of bone tissue resulting in decreased bone strength tissue resulting in decreased bone strength which predisposes to an increased risk of which predisposes to an increased risk of fracturefracture

Bone strength = Bone density + Bone qualityBone strength = Bone density + Bone quality Bone mineral density (BMD) is usually used Bone mineral density (BMD) is usually used

as a surrogate to assess bone strengthas a surrogate to assess bone strength

Bone Mineral DensityBone Mineral Density

Fracture risk increases 2-3 times for each Fracture risk increases 2-3 times for each standard deviation below gender-matched standard deviation below gender-matched young adult meanyoung adult mean

T score = #standard deviations from gender-T score = #standard deviations from gender-matched young adult meanmatched young adult mean

Z score = #standard deviations from age and Z score = #standard deviations from age and gender-matched meangender-matched mean

T score best correlates with fracture riskT score best correlates with fracture risk

World Health OrganizationWorld Health OrganizationDefinitionsDefinitions

Normal – T score greater than or equal to -1.0Normal – T score greater than or equal to -1.0 Osteopenia – T score between -1.0 and -2.5Osteopenia – T score between -1.0 and -2.5 Osteoporosis – T score less than or equal to Osteoporosis – T score less than or equal to

-2.5-2.5 Established osteoporosis – T score < -2.5 and Established osteoporosis – T score < -2.5 and

at least one fragility fractureat least one fragility fracture

PathophysiologyPathophysiology

Balance between bone resorption and Balance between bone resorption and formation (remodeling)formation (remodeling) Remodeling is in balance until about age 50Remodeling is in balance until about age 50

Osteoclasts resorb boneOsteoclasts resorb bone Osteoblasts form boneOsteoblasts form bone Estrogen inhibits osteoclastic bone resorptionEstrogen inhibits osteoclastic bone resorption Peak bone mass is established by age 20 for Peak bone mass is established by age 20 for

the hip and during the early 30’s for the spinethe hip and during the early 30’s for the spine


Women have increased incidence of osteoporosis Women have increased incidence of osteoporosis compared to men due to:compared to men due to:

Lower peak bone massLower peak bone mass Greater bone loss after menopause (10% bone loss)Greater bone loss after menopause (10% bone loss)

Men and non-white women have higher peak bone Men and non-white women have higher peak bone mass than white womenmass than white women

Genetic factors – 70-80% of peak bone mass is Genetic factors – 70-80% of peak bone mass is genetically determinedgenetically determined

Pregnancy and lactation cause transient bone lossPregnancy and lactation cause transient bone loss


Bone qualityBone quality Disruption of microarchitectural elements of Disruption of microarchitectural elements of

trabecular bonetrabecular bone Cortical thinningCortical thinning Decrease in degree of mineralizationDecrease in degree of mineralization

May be important in the futureMay be important in the future

Types of OsteoporosisTypes of Osteoporosis

Primary osteoporosisPrimary osteoporosis Related to aging and/or decreased gonadal Related to aging and/or decreased gonadal

functionfunction Aging bone loss is slower than menopausalAging bone loss is slower than menopausal Menopause related bone loss lasts about 10 yrsMenopause related bone loss lasts about 10 yrs

Secondary osteoporosisSecondary osteoporosis Due to medications or chronic illnesses that Due to medications or chronic illnesses that

accelerate bone lossaccelerate bone loss Consider secondary osteoporosis if Z-score is lowConsider secondary osteoporosis if Z-score is low

Chronic DiseasesChronic Diseases Cushing’s syndromeCushing’s syndrome HyperparathyroidismHyperparathyroidism HyperthyroidismHyperthyroidism Multiple myelomaMultiple myeloma LymphomaLymphoma Chronic liver diseaseChronic liver disease Chronic renal diseaseChronic renal disease Malabsorption syndromesMalabsorption syndromes Paraplegics, quadriplegicsParaplegics, quadriplegics HypogonadismHypogonadism

Anorexia nervosaAnorexia nervosa Athletic amenorrheaAthletic amenorrhea Diabetes mellitusDiabetes mellitus HemochromatosisHemochromatosis HyperprolactinemiaHyperprolactinemia Osteogenesis imperfectaOsteogenesis imperfecta Rheumatoid arthritisRheumatoid arthritis LupusLupus Psoriatic arthritisPsoriatic arthritis Vitamin D and Calcium Vitamin D and Calcium

deficiencydeficiency

MedicationsMedications GlucocorticoidsGlucocorticoids LithiumLithium ChemotherapyChemotherapy GnRH agonistGnRH agonist AnticonvulsantsAnticonvulsants

PhenobarbitalPhenobarbital DilantinDilantin TegretolTegretol ValproateValproate

MethotrexateMethotrexate SSRIsSSRIs

Prolonged heparin useProlonged heparin use Coumadin (?)Coumadin (?) Cyclosporine (?)Cyclosporine (?) Aromatase inhibitorsAromatase inhibitors Excess thyroid hormoneExcess thyroid hormone MedroxyprogesteroneMedroxyprogesterone Vitamin AVitamin A Proton pump inhibitorsProton pump inhibitors

Case #1Case #1

70 year old female presents with a new 70 year old female presents with a new vertebral compression fracture after slipping vertebral compression fracture after slipping on the ice. She has never had BMD testing.on the ice. She has never had BMD testing.

PMHPMH HTNHTN HyperlipidemiaHyperlipidemia GERDGERD DepressionDepression

Case #1Case #1

MEDSMEDS LisinoprilLisinopril ZocorZocor Protonix Protonix CelexaCelexa

Family hx – No hx osteoporosis knownFamily hx – No hx osteoporosis known Social hx – Non-smoker, no ETOHSocial hx – Non-smoker, no ETOH

Case #1Case #1

Should her SSRI be stopped?Should her SSRI be stopped? Should her PPI be stopped?Should her PPI be stopped? Should she have received BMD testing prior to Should she have received BMD testing prior to

starting these meds?starting these meds?

SSRIs and OsteoporosisSSRIs and Osteoporosis

Canadian Multicenter Osteoporosis Trial – Canadian Multicenter Osteoporosis Trial – 20062006 Prospective cohort of 5008 adults 50 years old or Prospective cohort of 5008 adults 50 years old or

greater, followed over 5 years for fracturesgreater, followed over 5 years for fractures 137 were on SSRIs137 were on SSRIs Risk of fragility fracture was increased 2 fold for Risk of fragility fracture was increased 2 fold for

pts on SSRIs pts on SSRIs Relative risk = 2.1 (1.3-3.4)Relative risk = 2.1 (1.3-3.4) Relative risk for corticosteroids = 1.33-2.6Relative risk for corticosteroids = 1.33-2.6

Study did not evaluate duration of SSRI useStudy did not evaluate duration of SSRI use

PPIs and OsteoporosisPPIs and Osteoporosis Prospective trial – (Roux 1/09)Prospective trial – (Roux 1/09)

1211 post-menopausal women1211 post-menopausal women For women on omeprazole the relative risk for vertebral For women on omeprazole the relative risk for vertebral

fractures was 3.5 (1.14-8.44)fractures was 3.5 (1.14-8.44) Need more studiesNeed more studies FDA recommends considering shorter duration or FDA recommends considering shorter duration or

lower dose of PPIlower dose of PPI PPI may interfere with calcium absorptionPPI may interfere with calcium absorption

Consider calcium citrate supplementationConsider calcium citrate supplementation No studies on initial BMD testing prior to starting No studies on initial BMD testing prior to starting

medmed

Case #2Case #2

16 year old female presents for discussion of 16 year old female presents for discussion of birth control options.birth control options.

PMH – NonePMH – None Family hx – No hx osteoporosisFamily hx – No hx osteoporosis Social hx – No smoking, ETOH or drugsSocial hx – No smoking, ETOH or drugs Pt really wants Depo Provera but her Mom is Pt really wants Depo Provera but her Mom is

concerned about side effects – she has heard concerned about side effects – she has heard that it weakens bones.that it weakens bones.

DepoProveraDepoProvera

Cross-sectional studies show decreased BMD Cross-sectional studies show decreased BMD in Depo usersin Depo users

No studies have shown increased fracture risk No studies have shown increased fracture risk with depo-userswith depo-users

Bone mass increases with cessation of DepoBone mass increases with cessation of Depo FDA recommends stopping Depo after 2 years FDA recommends stopping Depo after 2 years

unless no other viable birth control optionsunless no other viable birth control options FDA suggests evaluating BMD for use greater FDA suggests evaluating BMD for use greater

than 2 yearsthan 2 years

History – Risk FactorsHistory – Risk Factors

History of fractures, esp. vertebra, hip or wristHistory of fractures, esp. vertebra, hip or wrist Family history of osteoporosis or fragility fxs.Family history of osteoporosis or fragility fxs. Menstrual history – history of estrogen Menstrual history – history of estrogen

deficiencydeficiency NutritionNutrition ExerciseExercise Habits – tobacco, alcohol and caffeine useHabits – tobacco, alcohol and caffeine use

History and Physical ExamHistory and Physical Exam

No reliable history or physical findings to No reliable history or physical findings to identify patients with osteoporosisidentify patients with osteoporosis

Look for risk factors and signs of occult Look for risk factors and signs of occult vertebral fracturesvertebral fractures

Look for possible secondary causes of Look for possible secondary causes of osteoporosisosteoporosis

Consider further laboratory tests only if signs Consider further laboratory tests only if signs of a secondary causeof a secondary cause

History – Vertebral FracturesHistory – Vertebral Fractures

Back pain – acute or chronicBack pain – acute or chronic Loss of height (>1 inch)Loss of height (>1 inch) Restrictive lung disease symptoms (exertional Restrictive lung disease symptoms (exertional

dyspnea, decreased exercise tolerance)dyspnea, decreased exercise tolerance) Symptoms of reduced abdominal cavity (early Symptoms of reduced abdominal cavity (early

satiety)satiety) Symptoms of depression, anxiety and fearSymptoms of depression, anxiety and fear

Physical ExamPhysical Exam

Measure height and body weightMeasure height and body weight Look for spinal tenderness and deformities Look for spinal tenderness and deformities

(dowager’s hump)(dowager’s hump) Look for tooth lossLook for tooth loss Look for protuberant abdomenLook for protuberant abdomen Signs of secondary osteoporosisSigns of secondary osteoporosis Consider home visit to assess risk for falling Consider home visit to assess risk for falling

Risk Factors for OsteoporosisRisk Factors for Osteoporosis

Non-modifiableNon-modifiable Female genderFemale gender Increased ageIncreased age White or Asian raceWhite or Asian race Family history of osteoporosisFamily history of osteoporosis Personal history of fracturePersonal history of fracture Previous hyperthyroidismPrevious hyperthyroidism Rheumatoid arthritisRheumatoid arthritis Secondary osteoporosisSecondary osteoporosis

Risk Factors for OsteoporosisRisk Factors for Osteoporosis

ModifiableModifiable Tobacco useTobacco use Sedentary lifestyleSedentary lifestyle Caffeine use (tea is OK)Caffeine use (tea is OK) Low calcium and vitamin D intakeLow calcium and vitamin D intake Alcohol use (> 2 drinks per day)Alcohol use (> 2 drinks per day) Hormone deficiency statesHormone deficiency states Low weight (BMI<21)Low weight (BMI<21) Elevated homocysteine levelsElevated homocysteine levels Corticosteroid use (5 mg prednisone daily for 3 months)Corticosteroid use (5 mg prednisone daily for 3 months)

Risk Factors for FracturesRisk Factors for Fractures

History of fallingHistory of falling Poor physical conditionPoor physical condition Neurological disordersNeurological disorders Impaired vision and hearingImpaired vision and hearing Certain meds – sedatives, anti-hypertensivesCertain meds – sedatives, anti-hypertensives Environmental hazardsEnvironmental hazards

Environment ModificationEnvironment Modification

Remove throw rugsRemove throw rugs Decrease clutterDecrease clutter Handrails on stairsHandrails on stairs Improve lighting, night lightsImprove lighting, night lights Handrails in tubs and showers, non-skid surfacesHandrails in tubs and showers, non-skid surfaces Cane or walker if neededCane or walker if needed Consider hip protectorsConsider hip protectors Wear supportive, low-heeled shoesWear supportive, low-heeled shoes Tape down electric cordsTape down electric cords

Case #3Case #3

63 year old female presents for a physical63 year old female presents for a physical PMHPMH

HTNHTN GERDGERD AnxietyAnxiety

MedsMeds MetoprololMetoprolol OmeprazoleOmeprazole

Case #3Case #3

Social hx – smokes 1ppd, minimal ETOHSocial hx – smokes 1ppd, minimal ETOH Family hx – No osteoporosis or hip fracturesFamily hx – No osteoporosis or hip fractures BMI = 23, Ht = 5-4BMI = 23, Ht = 5-4 Should she be screened for osteoporosis?Should she be screened for osteoporosis?

Screening – Who to Screen?Screening – Who to Screen?

No studies showing decreased fracture risk No studies showing decreased fracture risk with screeningwith screening

However:However: Good evidence for increasing risk of osteoporosis Good evidence for increasing risk of osteoporosis

and fracture with ageand fracture with age Good evidence that bone mineral density Good evidence that bone mineral density

accurately predicts fracture risk (RR=2.6 for -1SD)accurately predicts fracture risk (RR=2.6 for -1SD) Good evidence that treating asymptomatic women Good evidence that treating asymptomatic women

with osteoporosis decreases fracture riskwith osteoporosis decreases fracture risk


US Preventive Services Task Force US Preventive Services Task Force recommendations based on current evidencerecommendations based on current evidence Screen all women > or equal to 65 yearsScreen all women > or equal to 65 years Screen women 60-65 yrs. if at increased riskScreen women 60-65 yrs. if at increased risk

Lower body wt. is best predictor of low BMDLower body wt. is best predictor of low BMD Consider using FRAXConsider using FRAX

Grade B recommendations – fair to good evidence Grade B recommendations – fair to good evidence to support recommendation, benefits outweigh to support recommendation, benefits outweigh risksrisks


USPSTF recommendations continuedUSPSTF recommendations continued No recommendations for or against routine No recommendations for or against routine

screening in women <60 yrs. or women 60-64 yrs. screening in women <60 yrs. or women 60-64 yrs. with no increased riskwith no increased risk

Screening women at lower risk for osteoporosis Screening women at lower risk for osteoporosis can identify additional women who might benefit can identify additional women who might benefit from treatment but would prevent smaller # from treatment but would prevent smaller # fractures.fractures.

Grade C recommendation – balance of benefits to Grade C recommendation – balance of benefits to harms is too close to make recommendationharms is too close to make recommendation


USPSTF guidelines agree with guidelines of USPSTF guidelines agree with guidelines of the National Osteoporosis Foundation and the the National Osteoporosis Foundation and the American Association of Clinical American Association of Clinical EndocrinologistsEndocrinologists

All recommend screening only if results will All recommend screening only if results will influence treatmentinfluence treatment If patient not in favor of treatment, DON’T If patient not in favor of treatment, DON’T

SCREEN!SCREEN!

Screening in MenScreening in Men

National Osteoporosis FoundationNational Osteoporosis Foundation Recommends screening all men over age 70 Recommends screening all men over age 70

regardless of risk factorsregardless of risk factors Evaluate for risk factors and discuss calcium and Evaluate for risk factors and discuss calcium and

vitamin D intake in all men >50vitamin D intake in all men >50 Screen men ages 50-69 with risk factorsScreen men ages 50-69 with risk factors However, very little evidence for or against However, very little evidence for or against

screening menscreening men

Screening DisadvantagesScreening Disadvantages

CostCost Potential radiation exposurePotential radiation exposure Potential unnecessary treatment for false Potential unnecessary treatment for false

positive or misinterpreted resultspositive or misinterpreted results Increased anxiety and perceived vulnerability Increased anxiety and perceived vulnerability

– can lead to increase in sedentary habits– can lead to increase in sedentary habits

Risk Factor AssessmentRisk Factor Assessment

Which are best at predicting osteoporotic Which are best at predicting osteoporotic fractures?fractures?

May help decide who to screenMay help decide who to screen


Age, weight and history of previous fracture Age, weight and history of previous fracture correlate the best with low BMDcorrelate the best with low BMD

FRAX = Fracture Risk Assessment toolFRAX = Fracture Risk Assessment tool Developed by WHO – 2008Developed by WHO – 2008 Estimates 10 year probability of major Estimates 10 year probability of major

osteoporotic fractures and hip fractureosteoporotic fractures and hip fracture www.shef.ac.uk/FRAX/www.shef.ac.uk/FRAX/


FRAXFRAX AgeAge GenderGender Prior fracturePrior fracture Low BMILow BMI Oral steroidsOral steroids Rheumatoid arthritisRheumatoid arthritis Secondary osteoporosis Secondary osteoporosis Parental hx of hip fractureParental hx of hip fracture SmokingSmoking ETOHETOH

Case #3Case #3

Decision is made to screen this patientDecision is made to screen this patient Which test is the best test?Which test is the best test?

Screening – Which Test?Screening – Which Test?

Conventional x-rays – osteopenia not detected Conventional x-rays – osteopenia not detected until bone mass 40% decreaseduntil bone mass 40% decreased

Bone turnover markers – experimental, Bone turnover markers – experimental, expensive and no good evidence to support use expensive and no good evidence to support use (human osteocalcin, bone alkaline (human osteocalcin, bone alkaline phosphatase)phosphatase) High false positive rateHigh false positive rate


All tests below have equivalent fracture risk All tests below have equivalent fracture risk predictabilitypredictability Dual-energy x-ray absorptiometry (DEXA)Dual-energy x-ray absorptiometry (DEXA) Quantitative CTQuantitative CT Calcaneal ultrasonographyCalcaneal ultrasonography


Calcaneal ultrasonographyCalcaneal ultrasonography Usually tests calcaneus onlyUsually tests calcaneus only Reflects other aspects of bone qualityReflects other aspects of bone quality More portable testMore portable test No radiationNo radiation Low costLow cost Low precisionLow precision Difficult to apply measurements to treatment Difficult to apply measurements to treatment

protocolsprotocols


Quantitative CTQuantitative CT Usually tests spine and hipUsually tests spine and hip High radiationHigh radiation High costHigh cost Good precisionGood precision


DEXADEXA Best validated test in studies and therefore Best validated test in studies and therefore

considered gold standardconsidered gold standard Results vary by 6-15% when using machines from Results vary by 6-15% when using machines from

different manufacturersdifferent manufacturers Usually test spine, hip or wrist (lateral spine)Usually test spine, hip or wrist (lateral spine) Low radiationLow radiation Intermediate costIntermediate cost Excellent precision – best if same machine is used Excellent precision – best if same machine is used

and same technicianand same technician


DEXADEXA HOWEVER……HOWEVER……

DEXA identifies fewer than half the people that go on DEXA identifies fewer than half the people that go on to have an osteoporotic fractureto have an osteoporotic fracture

Case #3Case #3

Her DEXA reveals a T-score = -1.5Her DEXA reveals a T-score = -1.5 When should she be retested if at all?When should she be retested if at all?

Screening – How Often?Screening – How Often?

Screening more often than every 2 years will Screening more often than every 2 years will not show accurate change in BMDnot show accurate change in BMD

Repeat screening more likely to be beneficial Repeat screening more likely to be beneficial in older women and women with risk factorsin older women and women with risk factors

No evidence about follow-up BMD testing No evidence about follow-up BMD testing after initiation of treatmentafter initiation of treatment NOF recommends follow-up BMD every 2 years NOF recommends follow-up BMD every 2 years

on treatmenton treatment

Screening SummaryScreening Summary

Screen all high risk womenScreen all high risk women Women > 64Women > 64 Women < 65 with significant risk factorsWomen < 65 with significant risk factors Men with risk factorsMen with risk factors

Screen every 2 yearsScreen every 2 years Consider using risk assessment tools to Consider using risk assessment tools to

determine high riskdetermine high risk DEXA scan is best test (BUT not perfect)DEXA scan is best test (BUT not perfect)

Case #3Case #3

She gets repeat screening with DEXA in two She gets repeat screening with DEXA in two years and the T-score is now -2.5years and the T-score is now -2.5

Does she need evaluation for secondary causes Does she need evaluation for secondary causes of osteoporosis?of osteoporosis?

Evaluating for Secondary Evaluating for Secondary OsteoporosisOsteoporosis

AACEAACE CBCCBC CMPCMP Ca, PhosCa, Phos 24 hour urine for Ca, Na, creatinine excretion24 hour urine for Ca, Na, creatinine excretion 25-hydroxyvitamin D level25-hydroxyvitamin D level

Above eval detects 90% of secondary Above eval detects 90% of secondary osteoporosisosteoporosis

Case #4Case #4

71 year old female presents for a review of her 71 year old female presents for a review of her DEXA results which reveal a T-score of -2.0. DEXA results which reveal a T-score of -2.0. She has no hx of fractures and no family hx of She has no hx of fractures and no family hx of fractures. She does not smoke. Her BMI=25.fractures. She does not smoke. Her BMI=25.

Do you tell her she has osteoporosis?Do you tell her she has osteoporosis? Are her results normal?Are her results normal? Do you recommend treatment for osteoporosis Do you recommend treatment for osteoporosis

and if so what?and if so what?

Who to Treat?Who to Treat?

Definite reduction in fractures for treatment of Definite reduction in fractures for treatment of BMD <-2.5 and for pts with history of fragility BMD <-2.5 and for pts with history of fragility fracturesfractures

Is there any benefit in treating anyone else?Is there any benefit in treating anyone else?

What About Osteopenia?What About Osteopenia?

T score between -1.0 and -2.5T score between -1.0 and -2.5 RCTs show no reduction in fracture risk for RCTs show no reduction in fracture risk for

patients with T scores -1.6 to -2.5patients with T scores -1.6 to -2.5 Individualize managementIndividualize management Decrease modifiable risk factorsDecrease modifiable risk factors

Increase calcium and vitamin D intakeIncrease calcium and vitamin D intake Increase exerciseIncrease exercise Decrease tobacco, alcohol and caffeine useDecrease tobacco, alcohol and caffeine use

What About Osteopenia?What About Osteopenia?

Use FRAX calculatorUse FRAX calculator If assessed risk of hip fracture is >3% for the next If assessed risk of hip fracture is >3% for the next

ten years, consider treatmentten years, consider treatment If risk of major osteoporotic fracture (wrist, If risk of major osteoporotic fracture (wrist,

vertebral, hip or proximal humerus) is >20% for vertebral, hip or proximal humerus) is >20% for the next ten years, consider treatmentthe next ten years, consider treatment

Using this calculator most pts with osteopenia will Using this calculator most pts with osteopenia will not be treatednot be treated

No actual studies on outcomes using FRAXNo actual studies on outcomes using FRAX www.shef.ac.uk/FRAX/www.shef.ac.uk/FRAX/

Treatment OptionsTreatment Options

ExerciseExercise Calcium and Vitamin DCalcium and Vitamin D EstrogenEstrogen BisphosphonatesBisphosphonates RaloxifeneRaloxifene CalcitoninCalcitonin Parathyroid hormoneParathyroid hormone

Case #5Case #5

65 year old, very healthy female has just found 65 year old, very healthy female has just found out she has osteoporosis. She does not want to out she has osteoporosis. She does not want to “pollute her body with chemicals” and will “pollute her body with chemicals” and will only use “natural remedies”only use “natural remedies”

What do you recommend?What do you recommend?

ExerciseExercise

Weight-bearing activity – walking, running, Weight-bearing activity – walking, running, aerobics, stair-climbing, strength training, aerobics, stair-climbing, strength training, dancing, court and field sportsdancing, court and field sports

No data on cycling, skating or skiingNo data on cycling, skating or skiing Exercise 3x/week for 30-60 minutes durationExercise 3x/week for 30-60 minutes duration Strength training reduces risk of falling alsoStrength training reduces risk of falling also Short term exercise increases BMD by 2% in Short term exercise increases BMD by 2% in

meta-analysis of 16 trialsmeta-analysis of 16 trials

ExerciseExercise

Cochrane review 2002Cochrane review 2002 18 RCTs of BMD in postmenopausal women18 RCTs of BMD in postmenopausal women Increased BMD of spine with any exerciseIncreased BMD of spine with any exercise Increased BMD of hip with walkingIncreased BMD of hip with walking

Meta-analysis 4/2004 (Kelley, et al)Meta-analysis 4/2004 (Kelley, et al) 143 premenopausal women143 premenopausal women Resistance exercise did not increase or maintain Resistance exercise did not increase or maintain

BMDBMD

Calcium and Vitamin DCalcium and Vitamin D

Randomized controlled trials show improved Randomized controlled trials show improved BMD and decreased fractures with comboBMD and decreased fractures with combo

NNT = 48 to prevent one hip fracture after 1.5 NNT = 48 to prevent one hip fracture after 1.5 years of treatmentyears of treatment

Need 1200 mg Ca/day and 800 IU vit. D/dayNeed 1200 mg Ca/day and 800 IU vit. D/day Calcium better absorbed if taken with food and Calcium better absorbed if taken with food and

600 mg or less at a time600 mg or less at a time Cost = $5/monthCost = $5/month


Calcium citrate is slightly better absorbed than Calcium citrate is slightly better absorbed than Ca carbonateCa carbonate

Consider using Ca citrate if patient on acid Consider using Ca citrate if patient on acid blocker medblocker med Ca carbonate – Oscal, Caltrate, Tums, ViactivCa carbonate – Oscal, Caltrate, Tums, Viactiv Ca citrate - CitracalCa citrate - Citracal


Side effects of calcium include dyspepsia, gas, Side effects of calcium include dyspepsia, gas, bloating and constipation(10%)bloating and constipation(10%)

May interfere with absorption of tetracycline or May interfere with absorption of tetracycline or quinolonesquinolones

If history of kidney stones evaluate for hypercalciuria If history of kidney stones evaluate for hypercalciuria prior to giving calciumprior to giving calcium

Recent meta-analysis based on WHI showed slight Recent meta-analysis based on WHI showed slight increase in MI and stroke in pts taking Ca with or increase in MI and stroke in pts taking Ca with or without vitamin D (Bolland 4/11)without vitamin D (Bolland 4/11) RR of MI = 1.24 (1.07-1.45)RR of MI = 1.24 (1.07-1.45)

CalciumCalcium

Cochrane review – 2004Cochrane review – 2004 15 RCTs, 1806 subjects15 RCTs, 1806 subjects Small improvement in bone density after 2-3 yrsSmall improvement in bone density after 2-3 yrs Trend toward decrease in vertebral fracturesTrend toward decrease in vertebral fractures Unclear if calcium alone decreases non-vertebral Unclear if calcium alone decreases non-vertebral

fracturesfractures

Vitamin DVitamin D

Vitamin D deficiencyVitamin D deficiency Decreased calcium absorptionDecreased calcium absorption PTH-mediated increase in bone resorptionPTH-mediated increase in bone resorption Decreased muscle strength and increased fallsDecreased muscle strength and increased falls

Vitamin DVitamin D

Cochrane review – April 2009Cochrane review – April 2009 Vitamin D alone showed no sig. effect on hip or Vitamin D alone showed no sig. effect on hip or

vertebral fracture ratevertebral fracture rate Vitamin D with calcium slightly reduced non-Vitamin D with calcium slightly reduced non-

vertebral fractures, but no effect on vertebral vertebral fractures, but no effect on vertebral fracturesfractures

No evidence that analogs of vitamin D offer any No evidence that analogs of vitamin D offer any advantage over native vitamin Dadvantage over native vitamin D

Vitamin D2 and vitamin D3 equally effective Vitamin D2 and vitamin D3 equally effective

Vitamin DVitamin D

National Osteoporosis FoundationNational Osteoporosis Foundation Recommends 800 – 1000 IU dailyRecommends 800 – 1000 IU daily Consider testing in pts at risk for deficiencyConsider testing in pts at risk for deficiency

ElderlyElderly Malabsorption diseasesMalabsorption diseases Chronic kidney diseaseChronic kidney disease Housebound patientsHousebound patients

Test serum 25(OH)D level should be between 30-Test serum 25(OH)D level should be between 30-60 (toxicity > 100)60 (toxicity > 100)

Folate and Vitamin B12Folate and Vitamin B12

RCT (Sato – 3/2005)RCT (Sato – 3/2005) 628 pts, s/p stroke628 pts, s/p stroke 5 mg folate and 1500 mcg of B12 vs placebo5 mg folate and 1500 mcg of B12 vs placebo Decreased hip fractures in treated groupDecreased hip fractures in treated group NNT = 14NNT = 14

MagnesiumMagnesium

Often taken by patientsOften taken by patients No studies show decrease in fracture rate or No studies show decrease in fracture rate or

increase in BMDincrease in BMD

PhytoestrogensPhytoestrogens

Act as weak estrogens but also have anti-Act as weak estrogens but also have anti-estrogen effectsestrogen effects

Primary source of phytoestrogens is Primary source of phytoestrogens is isoflavones which are found in soybeans(less isoflavones which are found in soybeans(less in tofu) and lignans (flaxseed; some cereals, in tofu) and lignans (flaxseed; some cereals, fruit, vegetables, and legumes)fruit, vegetables, and legumes)

Secondary sources are black cohosh and red Secondary sources are black cohosh and red cloverclover

PhytoestrogensPhytoestrogens

Small studies show some decrease in hot Small studies show some decrease in hot flushes and vaginal drynessflushes and vaginal dryness

No human studies showing effect on boneNo human studies showing effect on bone Dosage, purity, and adverse effects unknownDosage, purity, and adverse effects unknown Estreven and Remifemin are combinations of Estreven and Remifemin are combinations of

isoflavones, black cohosh and red cloverisoflavones, black cohosh and red clover

Estrogen Replacement TherapyEstrogen Replacement Therapy

WHI (Women’s Health Initiative Study)WHI (Women’s Health Initiative Study) NNT = 2000 to prevent one hip fracture after 5 NNT = 2000 to prevent one hip fracture after 5

years of treatmentyears of treatment Not as effective for treatment but has definite Not as effective for treatment but has definite

benefit for preventionbenefit for prevention Strongest benefit for ERT is for women < 60Strongest benefit for ERT is for women < 60 HERS showed no sig. decrease in fracture rate HERS showed no sig. decrease in fracture rate

over 4 yearsover 4 years FDA approved only for preventionFDA approved only for prevention

ERTERT

Transdermal and oral forms equally effectiveTransdermal and oral forms equally effective MUST use progesterone with estrogen if MUST use progesterone with estrogen if

patient has intact uteruspatient has intact uterus Estrogen with or without progesterone is Estrogen with or without progesterone is

equally as effectiveequally as effective Cost = $14-28/monthCost = $14-28/month Secondary benefit of decreasing menopausal Secondary benefit of decreasing menopausal

symptomssymptoms

ERT - HarmsERT - Harms

WHI studyWHI study Small increased risk of 22% for cardiovascular Small increased risk of 22% for cardiovascular

events (7 additional cases/10,000/yr)events (7 additional cases/10,000/yr) 26% increased risk of invasive breast cancer (8 26% increased risk of invasive breast cancer (8

additional cases/10,000/yr)additional cases/10,000/yr) 41% increased risk of stroke (8 additional 41% increased risk of stroke (8 additional

cases/10,000/yr)cases/10,000/yr) 2-fold increased risk of pulmonary embolism2-fold increased risk of pulmonary embolism SE’s – Vag. Bleeding, nausea, headache, mood SE’s – Vag. Bleeding, nausea, headache, mood

alterations, breast tenderness, bloatingalterations, breast tenderness, bloating

BisphosphonatesBisphosphonates

Work by inhibiting osteoclastic activityWork by inhibiting osteoclastic activity RCT’s show significant and rapid reduction in RCT’s show significant and rapid reduction in

fracture risk for women with previous fracture fracture risk for women with previous fracture and osteoporosisand osteoporosis

Evidence not as good for women without Evidence not as good for women without previous fractureprevious fracture

Alendronate (Fosamax)Alendronate (Fosamax)

NNT = 34 to prevent one vert. fx over 3 yrs.NNT = 34 to prevent one vert. fx over 3 yrs. NNT = 86 to prevent one hip fx over 3 yrs.NNT = 86 to prevent one hip fx over 3 yrs. Dose = 5-10 mg/day or 35-70 mg/weekDose = 5-10 mg/day or 35-70 mg/week Forms – oral solution, Fosamax with D weeklyForms – oral solution, Fosamax with D weekly Cost = $95/monthCost = $95/month SE’s – nausea, dyspepsia, esophageal ulcer, SE’s – nausea, dyspepsia, esophageal ulcer,

esophagitisesophagitis Weekly dosing showed equivalent increase in BMD Weekly dosing showed equivalent increase in BMD

to daily dosing (no data on fractures)to daily dosing (no data on fractures)

AlendronateAlendronate

Meta-analysis of RCTs – (Papapoulos – 5/05)Meta-analysis of RCTs – (Papapoulos – 5/05) Post-menopausal womenPost-menopausal women Dose = 5-10 mg/day for 1-4.5 yrsDose = 5-10 mg/day for 1-4.5 yrs Overall risk reduction for hip fractures of 55% in Overall risk reduction for hip fractures of 55% in

pts with osteoporosispts with osteoporosis Clinically sig decrease in hip fracturesClinically sig decrease in hip fractures

Risedronate (Actonel)Risedronate (Actonel)

NNT = 15 to prevent one vert. fx over 3 yrs.NNT = 15 to prevent one vert. fx over 3 yrs. NNT = 91 to prevent one hip fx over 3 yrs.NNT = 91 to prevent one hip fx over 3 yrs. Dose = 5 mg/day, 35 mg/week, 150 mg/monthDose = 5 mg/day, 35 mg/week, 150 mg/month Cost = $150/monthCost = $150/month SE’s – abdominal pain, nausea, diarrhea but SE’s – abdominal pain, nausea, diarrhea but

not sig. different from placebonot sig. different from placebo No sig. GI adverse events even in patients with No sig. GI adverse events even in patients with

history of ulcers, GERD, or taking NSAIDShistory of ulcers, GERD, or taking NSAIDS

RisedronateRisedronate

Cochrane systematic review – 8/2003Cochrane systematic review – 8/2003 8 RCTs8 RCTs Postmenopausal women received 5 mg/day, Postmenopausal women received 5 mg/day,

compared to Ca or placebocompared to Ca or placebo Increased BMD after 3 yrsIncreased BMD after 3 yrs Decreased vertebral and non-vertebral fracturesDecreased vertebral and non-vertebral fractures No difference in side effects compared to placeboNo difference in side effects compared to placebo

Ibandronate (Boniva)Ibandronate (Boniva)

BONE study – (Delmas – 9/2003)BONE study – (Delmas – 9/2003) Large multi-national RCTLarge multi-national RCT Oral Ibandronate Osteoporosis Vertebral Fracture Oral Ibandronate Osteoporosis Vertebral Fracture

Trial in N. America and EuropeTrial in N. America and Europe 2946 post-menopausal women2946 post-menopausal women Daily or intermittent ibandronate vs placeboDaily or intermittent ibandronate vs placebo Decreased risk for vertebral fractures by 50-62%Decreased risk for vertebral fractures by 50-62% NO decreased risk of non-vertebral fracturesNO decreased risk of non-vertebral fractures

Zoledronic Acid (Reclast)Zoledronic Acid (Reclast)

Given IV every 12 monthsGiven IV every 12 months Decreases both vertebral and hip fracturesDecreases both vertebral and hip fractures ExpensiveExpensive Consider only in certain high risk ptsConsider only in certain high risk pts


Less than 1% of each dose is absorbedLess than 1% of each dose is absorbed Optimize absorption by taking with full glass Optimize absorption by taking with full glass

of water and 30 mins prior to breakfastof water and 30 mins prior to breakfast Avoid GI problems by standing or sitting for Avoid GI problems by standing or sitting for

30 mins after taking med30 mins after taking med Do not use in patients with creatinine Do not use in patients with creatinine

clearance <30 ml/min or hypocalcemiaclearance <30 ml/min or hypocalcemia Accumulates in bone – long term effects Accumulates in bone – long term effects

unknownunknown


Does one work better than another?Does one work better than another? Head to head RCT of alendronate 70 mg/week and Head to head RCT of alendronate 70 mg/week and

risedronate 35 mg/week (Rosen-1/2005)risedronate 35 mg/week (Rosen-1/2005) Total of 1053 postmenopausal women with Total of 1053 postmenopausal women with

osteoporosis, studied over 12 monthsosteoporosis, studied over 12 months Alendronate showed greater increase in BMD Alendronate showed greater increase in BMD

compared to risedronatecompared to risedronate Fracture rate not assessedFracture rate not assessed Both drugs tolerated equally wellBoth drugs tolerated equally well

Case #6Case #6

72 year old female with T-score = -2.7 and no 72 year old female with T-score = -2.7 and no hx fracture.hx fracture.

You have recommended starting a You have recommended starting a bisphosphonate but she has heard that these bisphosphonate but she has heard that these drugs cause cancer and a jaw problem.drugs cause cancer and a jaw problem.

What do you say?What do you say?


Osteonecrosis of the jaw (ONJ)Osteonecrosis of the jaw (ONJ) Canadian Consensus Practice Guidelines (6/2008)Canadian Consensus Practice Guidelines (6/2008) ONJ has been clearly associated with use of high ONJ has been clearly associated with use of high

dose IV bisphosphonates in the treatment of cancerdose IV bisphosphonates in the treatment of cancer ONJ has NOT been clearly linked with low-dose ONJ has NOT been clearly linked with low-dose

bisphosphonates used for osteoporosisbisphosphonates used for osteoporosis Advise good oral hygiene and regular dental visitsAdvise good oral hygiene and regular dental visits Consider holding drug for non-emergent dental Consider holding drug for non-emergent dental

surgerysurgery


Atrial fibrillationAtrial fibrillation Systematic review – (Loke – 2009)Systematic review – (Loke – 2009)

Results of studies were mixedResults of studies were mixed There may be a link with bisphosphonates and atrial fib There may be a link with bisphosphonates and atrial fib

but data was too heterogeneous to make a determinationbut data was too heterogeneous to make a determination No increase in stroke risk or cardiovascular mortalityNo increase in stroke risk or cardiovascular mortality

FDA fells this is a chance findingFDA fells this is a chance finding


Subtrochanteric fractureSubtrochanteric fracture Occur after minimal or no traumaOccur after minimal or no trauma Direct etiologic relationship not yet substantiatedDirect etiologic relationship not yet substantiated

Esophageal cancerEsophageal cancer Incidence went from 1 case per 1000 in untreated Incidence went from 1 case per 1000 in untreated

pts to 2 cases per 1000 in those treated with pts to 2 cases per 1000 in those treated with bisphosphonates for 5 years or morebisphosphonates for 5 years or more

Consider drug holiday of 1-2 years after 3-5 Consider drug holiday of 1-2 years after 3-5 years of therapyyears of therapy

Case #7Case #7

75 year old female with hx osteoporotic 75 year old female with hx osteoporotic vertebral fx cannot tolerate the vertebral fx cannot tolerate the bisphosphonates. She has hx of severe GERD bisphosphonates. She has hx of severe GERD and peptic ulcer disease.and peptic ulcer disease.

What do you recommend?What do you recommend?

Selective Estrogen Receptor Selective Estrogen Receptor ModulatorsModulators

Raloxifene (Evista)Raloxifene (Evista) Blocks action of cytokines which stimulate Blocks action of cytokines which stimulate

bone resorptionbone resorption RCT’s show sig. decrease in new vertebral RCT’s show sig. decrease in new vertebral

fractures for women with previous history of fractures for women with previous history of fracture and osteoporosisfracture and osteoporosis

NNT = 29 to prevent one vert. fx over 3 yrs.NNT = 29 to prevent one vert. fx over 3 yrs. NO evidence of decrease in hip fracturesNO evidence of decrease in hip fractures

RaloxifeneRaloxifene

Dose = 60 mg/dayDose = 60 mg/day Cost = $150/monthCost = $150/month Secondary benefit may be reduction of breast Secondary benefit may be reduction of breast

cancer riskcancer risk SE’s – leg cramps(3%), hot flashes(6%), risk SE’s – leg cramps(3%), hot flashes(6%), risk

of venous thromboembolism (1 in 465 of venous thromboembolism (1 in 465 women/yr)women/yr)

Does not increase risk of endometrial Does not increase risk of endometrial hyperplasia or cancerhyperplasia or cancer

Salmon CalcitoninSalmon Calcitonin

Calcitonin nasal spray (Miacalcin)Calcitonin nasal spray (Miacalcin) Large RCT showed decreased new vertebral Large RCT showed decreased new vertebral

fractures in women with previous history of fractures in women with previous history of osteoporotic vertebral fx.osteoporotic vertebral fx.

No effect reported for hip fracturesNo effect reported for hip fractures No definite effect for women with no previous No definite effect for women with no previous

osteoporotic fx.osteoporotic fx. Increased BMD less than that seen with Increased BMD less than that seen with

bisphosphonates or estrogenbisphosphonates or estrogen

Salmon CalcitoninSalmon Calcitonin

Dose = 200 IU/day, 1 spray in 1 nostril qdDose = 200 IU/day, 1 spray in 1 nostril qd Cost = $112/monthCost = $112/month SE’s – rhinitis(5%), epistaxis, sinusitisSE’s – rhinitis(5%), epistaxis, sinusitis Alternate nostrils to decrease SE’sAlternate nostrils to decrease SE’s Secondary benefit of decreased pain from Secondary benefit of decreased pain from

vertebral fracturesvertebral fractures

Parathyroid HormoneParathyroid Hormone Stimulates bone formationStimulates bone formation Teriparatide (Forteo) – recombinant PTHTeriparatide (Forteo) – recombinant PTH RCT shows 1/3 decreased incidence of vert. fx and ½ RCT shows 1/3 decreased incidence of vert. fx and ½

decreased incidence of non-vert. fxdecreased incidence of non-vert. fx Dose = 20 mcg SC qdDose = 20 mcg SC qd Less convenientLess convenient More expensive - $1000/monthMore expensive - $1000/month SEs – nausea, headache, hypercalcemia, dizziness, SEs – nausea, headache, hypercalcemia, dizziness,

leg cramps, ? risk osteosarcomaleg cramps, ? risk osteosarcoma Measure Ca, vitamin D and PTH levels prior to Measure Ca, vitamin D and PTH levels prior to

treatmenttreatment

Parathyroid HormoneParathyroid Hormone

FDA black box warningFDA black box warning Teriparatide caused osteosarcoma in rats using Teriparatide caused osteosarcoma in rats using

much higher doses of the drugmuch higher doses of the drug Drug is contraindicated in pts at risk for Drug is contraindicated in pts at risk for

osteosarcomaosteosarcoma Pagets disease of bonePagets disease of bone Hx of irradiation involving the skeletonHx of irradiation involving the skeleton Unexplained elevation of alkaline phosphataseUnexplained elevation of alkaline phosphatase

Safety after 2 years duration is unknownSafety after 2 years duration is unknown


RCT – (Neer – 5/01)RCT – (Neer – 5/01) 1637 post-menopausal women with prior vertebral 1637 post-menopausal women with prior vertebral

fracturesfractures Average T-score = -2.6Average T-score = -2.6 20 or 40 mcg PTH vs placebo20 or 40 mcg PTH vs placebo NNT = 11 to prevent one vertebral fractureNNT = 11 to prevent one vertebral fracture 40 mcg dose worked a little better but had more 40 mcg dose worked a little better but had more

side effects (hypercalcemia)side effects (hypercalcemia)


RCT – (Body–10/02)RCT – (Body–10/02) 14 months duration14 months duration Compared PTH to alendronateCompared PTH to alendronate PTH increased BMD in hip and spine more than PTH increased BMD in hip and spine more than

alendronate (12.2% vs 5.6%)alendronate (12.2% vs 5.6%) Non-vertebral fracture rate was lower in the PTH Non-vertebral fracture rate was lower in the PTH

groupgroup

DenosumabDenosumab

Monoclonal antibody against RANKLMonoclonal antibody against RANKL Decreases osteoclastic activityDecreases osteoclastic activity Brand name – ProliaBrand name – Prolia 60 mg SQ every 6 months60 mg SQ every 6 months Studies show reduced fractures of the hip, Studies show reduced fractures of the hip,

spine and non-vertebral sitesspine and non-vertebral sites SEs – Skin infections, dermatitis, ? SEs – Skin infections, dermatitis, ?

osteonecrosis of the jawosteonecrosis of the jaw

Combination TherapyCombination Therapy

No studies demonstrating reduction in fracture No studies demonstrating reduction in fracture riskrisk

More improvement in BMD with combined More improvement in BMD with combined estrogen and alendronateestrogen and alendronate

RCT of combined PTH and alendronate RCT of combined PTH and alendronate showed no improvement over PTH alone showed no improvement over PTH alone (Finkelstein-2003)(Finkelstein-2003)

AACE does not recommend combined therapyAACE does not recommend combined therapy

Treatment MonitoringTreatment Monitoring

AACE guidelinesAACE guidelines DEXA every 1-2 years until stableDEXA every 1-2 years until stable BMD should be stable or increasing and there BMD should be stable or increasing and there

should be no fracturesshould be no fractures If this is not the case consider different treatmentIf this is not the case consider different treatment

Osteoporosis in MenOsteoporosis in Men

30% of hip fractures occur in males30% of hip fractures occur in males 1.5 million men >65 have osteoporosis1.5 million men >65 have osteoporosis May have higher mortality rate compared to May have higher mortality rate compared to

femalesfemales 2/3 have secondary osteoporosis2/3 have secondary osteoporosis

Hypogonadism, glucocorticoid use, etc.Hypogonadism, glucocorticoid use, etc. Risk increases with age but later than in Risk increases with age but later than in

womenwomen

Osteoporosis in MenOsteoporosis in Men

TreatmentTreatment 1000 mg/day calcium and 800 IU/day vitamin D1000 mg/day calcium and 800 IU/day vitamin D ExerciseExercise If hypogonadism, consider testosteroneIf hypogonadism, consider testosterone Bisphosphonates – RCT of alendronate 10 mg/day Bisphosphonates – RCT of alendronate 10 mg/day

showed sig increase in BMD and decrease in showed sig increase in BMD and decrease in vertebral fractures (Orwoll – 8/2000)vertebral fractures (Orwoll – 8/2000)

PTH – RCT of PTH 20mcg/day showed increased PTH – RCT of PTH 20mcg/day showed increased BMD (Orwoll – 1/2003)BMD (Orwoll – 1/2003)

Prevention SummaryPrevention Summary

Start adequate calcium and vitamin D intake in Start adequate calcium and vitamin D intake in childhoodchildhood

Encourage exerciseEncourage exercise Decrease risk factors for osteoporosisDecrease risk factors for osteoporosis Decrease risk factors for fallingDecrease risk factors for falling Consider bisphosphonate for prevention if Consider bisphosphonate for prevention if

high riskhigh risk

Treatment SummaryTreatment Summary

AACE recommendationsAACE recommendations 11stst line – alendronate, risedronate, zoledronic acid, line – alendronate, risedronate, zoledronic acid,

denosumabdenosumab 22ndnd line – ibandronate, raloxifene line – ibandronate, raloxifene Last line – calcitoninLast line – calcitonin Teriparatide only for pts that fail aboveTeriparatide only for pts that fail above No combination therapyNo combination therapy

ReferencesReferences

Prevention and Treatment of Osteoporosis in Postmenopausal Women. Prevention and Treatment of Osteoporosis in Postmenopausal Women. JFP October 2002JFP October 2002

Screening for Osteoporosis in Postmenopausal Women: Recommendations Screening for Osteoporosis in Postmenopausal Women: Recommendations and Rationale, US Preventive Services Task Force. Ann. Intern. Med. 17 and Rationale, US Preventive Services Task Force. Ann. Intern. Med. 17 Sept. 2002Sept. 2002

Radiologic Bone Assessment in the Eval. of Osteoporosis. AFP April Radiologic Bone Assessment in the Eval. of Osteoporosis. AFP April 20022002

Cauley, JA. Effects of HRT on clinical fractures and ht loss(HERS). Am J Cauley, JA. Effects of HRT on clinical fractures and ht loss(HERS). Am J Med. 2001.Med. 2001.

Papapoulos, SE. Meta-analysis of the efficacy of alendronate for the Papapoulos, SE. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporosis Int. prevention of hip fractures in postmenopausal women. Osteoporosis Int. 2005 May.2005 May.

Delmas, PD. Daily and intermittent oral ibandronate normalize bone Delmas, PD. Daily and intermittent oral ibandronate normalize bone turnover and reduce vertebral fracture risk: results from the BONE study. turnover and reduce vertebral fracture risk: results from the BONE study. Osteoporosis Int. 2004 April.Osteoporosis Int. 2004 April.


Calcium Supplements. The Medical Letter April 3, 2000Calcium Supplements. The Medical Letter April 3, 2000 Osteoporosis: Parts I and II AFP March 2001Osteoporosis: Parts I and II AFP March 2001 Cochrane DatabaseCochrane Database Petitti, DB. The WHO Study of Hormonal Contraception and Bone Health. Petitti, DB. The WHO Study of Hormonal Contraception and Bone Health.

Ob-Gyn. 2000 May.Ob-Gyn. 2000 May. Orr-Walker, BJ. The effect of past use of the injectable contraceptive depot Orr-Walker, BJ. The effect of past use of the injectable contraceptive depot

medroxyprog. acetate on bone mineral density in normal post-menopausal medroxyprog. acetate on bone mineral density in normal post-menopausal women. Clin Endocrinol. 1998 Nov.women. Clin Endocrinol. 1998 Nov.

Kelley, GA. Efficacy of resistance exercise on lumbar spine and femoral Kelley, GA. Efficacy of resistance exercise on lumbar spine and femoral neck BMD in premenopausal women: a meta-analysis. J Womens Health. neck BMD in premenopausal women: a meta-analysis. J Womens Health. 2004 April.2004 April.

Sato, Y. Effect of folate and mecobalamin on hip fractures in pts with Sato, Y. Effect of folate and mecobalamin on hip fractures in pts with stroke: a RCT. JAMA. 2005 March.stroke: a RCT. JAMA. 2005 March.


Bauer, DC. Use of statins and fracture: results of 4 prospective studies and Bauer, DC. Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. cumulative meta-analysis of observational studies and controlled trials. Arch Intern Med. 2004 Jan.Arch Intern Med. 2004 Jan.

Neer, RM. Effect of PTH on fractures and BMD in postmenopausal women Neer, RM. Effect of PTH on fractures and BMD in postmenopausal women with osteoporosis. N Engl J Med. 2001 Maywith osteoporosis. N Engl J Med. 2001 May

Body, JJ. A randomized double-blind trial to compare the efficacy of Body, JJ. A randomized double-blind trial to compare the efficacy of teriparatide with alendronate in postmenopausal women with osteoporosis. teriparatide with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002 Oct.J Clin Endocrinol Metab. 2002 Oct.

Orwoll, E. Alendronate for the treatment of osteoporosis in men. N Engl J Orwoll, E. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000 Aug.Med. 2000 Aug.

Orwoll, ES. The effect of teriparatide therapy in men with osteoporosis. J Orwoll, ES. The effect of teriparatide therapy in men with osteoporosis. J Bone Miner Res. 2003 Jan.Bone Miner Res. 2003 Jan.

AACE Guidelines for Diag and Treatment of Osteoporosis - 2010AACE Guidelines for Diag and Treatment of Osteoporosis - 2010

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Osteoporosis DeAnn Cummings, MD January 12, 2012