Osteoporosis/Osteopenia

OsteoporosisOsteoporosis

Capital Conference 2007Capital Conference 2007

Marc Childress, MDMarc Childress, MD

OsteoporosisOsteoporosis EpidemiologyEpidemiology Risk FactorsRisk Factors PreventionPrevention ScreeningScreening DiagnosisDiagnosis TreatmentTreatment Osteoporosis in MenOsteoporosis in Men ManagementManagement FallsFalls Acute ComplicationsAcute Complications

OsteoporosisOsteoporosis

Average female bone mineral density peaks Average female bone mineral density peaks at age 35, slow decline thereafterat age 35, slow decline thereafter

Density loss is accelerated post-menopausallyDensity loss is accelerated post-menopausally

EpidemiologyEpidemiology

1.3 million osteoporotic fractures in 1.3 million osteoporotic fractures in U.S. every year U.S. every year

40% of women over 50 have 40% of women over 50 have osteopeniaosteopenia

7% of women over 50 have 7% of women over 50 have osteoporosisosteoporosis

Presence of osteoporosis carries 4-Presence of osteoporosis carries 4-fold increase in fracture rate (over 50 fold increase in fracture rate (over 50 years old)years old)

EpidemiologyEpidemiology

Among those who Among those who live to 90 years old, live to 90 years old, 1/3 of women and 1/3 of women and 1/6 of men will have 1/6 of men will have sustained sustained osteoporotic osteoporotic fracturefracture

Hip fracture Hip fracture mortality at 1 year mortality at 1 year is approaching 25%is approaching 25%

Risk FactorsRisk Factors

Female GenderFemale Gender 3X more likely to have hip or vertebral 3X more likely to have hip or vertebral

fracture than menfracture than men 6X more likely to have forearm fracture6X more likely to have forearm fracture

Caucasian RaceCaucasian Race Higher than African-American, Asian Higher than African-American, Asian

racerace SmokingSmoking Low Body Weight (less than 58 kilos)Low Body Weight (less than 58 kilos)

Risk Factors (cont’d)Risk Factors (cont’d)

Sedentary LifestyleSedentary Lifestyle Excessive Alcohol IntakeExcessive Alcohol Intake

Ample suggestion that moderate alcohol Ample suggestion that moderate alcohol intake may be protectiveintake may be protective

No clear thresholdNo clear threshold Nursing Home ResidentsNursing Home Residents

10X more likely to experience hip 10X more likely to experience hip fracture than age-matched non-fracture than age-matched non-residents residents

Predisposing Medical Predisposing Medical ConditionsConditions

Estrogen DeficiencyEstrogen Deficiency Inflammatory Bowel Inflammatory Bowel

DiseaseDisease Type 2 Diabetes Type 2 Diabetes

Mellitus Mellitus Celiac diseaseCeliac disease Cystic fibrosisCystic fibrosis HyperthyroidismHyperthyroidism HyperparathyroidisHyperparathyroidis

mm

HypogonadismHypogonadism Liver DiseaseLiver Disease Corticosteroid useCorticosteroid use Heparin useHeparin use Cyclosporine useCyclosporine use Depo-Provera useDepo-Provera use Vitamin A Vitamin A

(systemic retinoid) (systemic retinoid) useuse

Risk Factors (cont’d)Risk Factors (cont’d)

No clear increase No clear increase in risk with in risk with carbonated carbonated beveragesbeverages Although unclear Although unclear

risk association risk association with excessive with excessive caffeinecaffeine

What they want you to What they want you to know…know…

Chronic excess thyroid hormone Chronic excess thyroid hormone replacement over a number of years in replacement over a number of years in post-menopausal women can lead to post-menopausal women can lead to

diffuse nontoxic goiterdiffuse nontoxic goiter osteoarthritisosteoarthritis osteoporosis hyperparathyroidismhyperparathyroidism

What they want you to What they want you to know…know…

A 31-year-old white female presents with her A 31-year-old white female presents with her third stress fracture of a lower extremity in third stress fracture of a lower extremity in the past 4 years. Her history and the past 4 years. Her history and examination are otherwise unremarkable examination are otherwise unremarkable except for a controlled seizure disorder. except for a controlled seizure disorder.

The most likely cause of her bone problem isThe most likely cause of her bone problem is

Addison’s diseaseAddison’s disease HypothyroidismHypothyroidism Osteogenesis imperfectaOsteogenesis imperfecta Anticonvulsive medicationAnticonvulsive medication

PreventionPrevention

Adequate total dietary calciumAdequate total dietary calcium 1500 mg/day for postmenopausal without HRT1500 mg/day for postmenopausal without HRT 1000-1200 mg/day premen, postmen with HRT1000-1200 mg/day premen, postmen with HRT

Vitamin DVitamin D 800 IU/day for postmenopausal800 IU/day for postmenopausal 400 IU/day premen, postmen with HRT400 IU/day premen, postmen with HRT

Regular weight-bearing exerciseRegular weight-bearing exercise Additional protective factors: increased Additional protective factors: increased

BMI, African-American ethnicity, BMI, African-American ethnicity, moderate EtOH intakemoderate EtOH intake

What they want you to What they want you to know…know…

Which of the following antihypertensives agents may help Which of the following antihypertensives agents may help preserve bone mineral density?preserve bone mineral density?

Atenolol (Tenormin)Atenolol (Tenormin) Doxazosin (Cardura)Doxazosin (Cardura) Enalapril (Vasotec)Enalapril (Vasotec) HydrochlorothiazideHydrochlorothiazide Nifedipine (Procardia, Adalat)Nifedipine (Procardia, Adalat)

Which one of the following is associated with a reduced Which one of the following is associated with a reduced risk of post-menopausal osteoporosis?risk of post-menopausal osteoporosis?

Corticosteroid useCorticosteroid use Cigarette smokingCigarette smoking Diuretic useDiuretic use Low BMILow BMI Asian EthnicityAsian Ethnicity

ScreeningScreening

USPTF/AAFPUSPTF/AAFP— “routine screening” — “routine screening” above the age of 65, consider above the age of 65, consider between 60-65 for increased riskbetween 60-65 for increased risk

National Osteoporosis Foundation—National Osteoporosis Foundation—recommend screening above 65, or recommend screening above 65, or in younger with risk factorsin younger with risk factors

Difficulty with recommendationsDifficulty with recommendations Cost issues Time interval of screening examination

Screening OptionsScreening Options Single Photon absorptiometrySingle Photon absorptiometry

-can only be used at radius or calcaneus -can only be used at radius or calcaneus (unclear attenuation source)(unclear attenuation source)

Dual Photon absorptiometryDual Photon absorptiometry -can be used at deeper sites (spine,hip)-can be used at deeper sites (spine,hip)

Screening OptionsScreening Options

Dual X-ray absorptiometry (DEXA)—Dual X-ray absorptiometry (DEXA)—MOST POPULARMOST POPULAR Pros:Pros:

-precise measurements at clinically relevant -precise measurements at clinically relevant sites (hip and spine)sites (hip and spine)

-minimal radiation-minimal radiation Cons:Cons:

-not portable-not portable -expensive-expensive

Screening OptionsScreening Options

Quantitative CTQuantitative CT Pros:Pros:

-similar accuracy to DEXA-similar accuracy to DEXA -may have slightly better predictive value in -may have slightly better predictive value in

risk of vertebral fracturerisk of vertebral fracture Cons:Cons:

-more expensive (than DEXA)-more expensive (than DEXA) -less reproducible (bigger variance)-less reproducible (bigger variance) -higher radiation-higher radiation

Screening OptionsScreening Options

UltrasoundUltrasound Pros:Pros:

-studies thus far have suggested similar predictive -studies thus far have suggested similar predictive ability of fracture to DEXAability of fracture to DEXA

-No radiation-No radiation -Portable-Portable

Cons:Cons: -unable to provide true Bone Density Measurements -unable to provide true Bone Density Measurements

(less applicable to current diagnostic standards and (less applicable to current diagnostic standards and treatment goals based on BMD)treatment goals based on BMD)

*current role in identifying high risk *current role in identifying high risk individuals, not in pervasive screening individuals, not in pervasive screening

DiagnosisDiagnosis

2 Methods2 Methods 1) Radiographic determination of Bone 1) Radiographic determination of Bone

Mineral Density to be Mineral Density to be

-1-1 Standard Deviations below young adult Standard Deviations below young adult reference mean-OSTEOPENIAreference mean-OSTEOPENIA

-2.5-2.5 Standard Deviations below young Standard Deviations below young adult reference mean-OSTEOPOROSISadult reference mean-OSTEOPOROSIS

2) Presence of fragility fracture (no 2) Presence of fragility fracture (no signif trauma hx, and absence of signif trauma hx, and absence of osteomalacia or bone tumor)osteomalacia or bone tumor)

TreatmentTreatment

BisphosphonatesBisphosphonates- most appropriate - most appropriate initial treatment for women with initial treatment for women with osteoporosisosteoporosis Alendronate (10 mg/day or 70 mg weekly),Alendronate (10 mg/day or 70 mg weekly),

-best when taken on empty stomach with 8 oz. -best when taken on empty stomach with 8 oz. water, standing upright for 30 minutes, risk of water, standing upright for 30 minutes, risk of esophagitis esophagitis

- contraindicated in patients with active upper - contraindicated in patients with active upper GI diseaseGI disease

Risedronate (5 mg/day or 35 mg weekly)Risedronate (5 mg/day or 35 mg weekly) -less apparent GI risk than alendronate-less apparent GI risk than alendronate

TreatmentTreatment

SERMS (Selective Estrogen SERMS (Selective Estrogen Receptor Modulators)-Receptor Modulators)- Raloxifene-best data among 2 in class, Raloxifene-best data among 2 in class,

approved for both prevention and approved for both prevention and treatment of osteoporosistreatment of osteoporosis

Tamoxifen—not FDA approved, but Tamoxifen—not FDA approved, but some data to suggest bone benefitsome data to suggest bone benefit

TreatmentTreatment

PTH (Teriparatide)PTH (Teriparatide)-daily injections. -daily injections. Currently limited to those at very high Currently limited to those at very high fracture risk or those unresponsive to fracture risk or those unresponsive to bisphosponate therapy due to high cost bisphosponate therapy due to high cost ($20/day) and risk of osteosarcoma($20/day) and risk of osteosarcoma

Calcitonin-Calcitonin- nasal spray. Less effect on bone nasal spray. Less effect on bone than bisphosphonates, risk of tachyphylaxis. than bisphosphonates, risk of tachyphylaxis. Unique role in acute treatment of Unique role in acute treatment of osteoporotic fracture—may be switched to osteoporotic fracture—may be switched to alternate therapy once pain diminished.alternate therapy once pain diminished.

TreatmentTreatment

Estrogen / Progestin therapyEstrogen / Progestin therapy No longer first line, but still an option in No longer first line, but still an option in

women who may be contraindicated from or women who may be contraindicated from or intolerant to bisphosponates or raloxifene.intolerant to bisphosponates or raloxifene.

Combination therapyCombination therapy- there are - there are demonstrable gains in using demonstrable gains in using bisphosponates in combination with bisphosponates in combination with SERMs, and estrogen therapy if no SERMs, and estrogen therapy if no contraindications and less than desired contraindications and less than desired benefit on single osteoporosis therapybenefit on single osteoporosis therapy

What they want you to What they want you to know…know…

Raloxifene (Evista) :Raloxifene (Evista) :

is used to manage hot flashesis used to manage hot flashes increases bone densityincreases bone density stimulates breast tissuestimulates breast tissue stimulates endometrial proliferationstimulates endometrial proliferation raises LDL and total cholesterol raises LDL and total cholesterol

levelslevels

Osteoporosis in MenOsteoporosis in Men --1.5 million men in U.S. with osteoporosis, 3.5 million at --1.5 million men in U.S. with osteoporosis, 3.5 million at

riskrisk --1 in 6 men at 90 years of age will experience hip --1 in 6 men at 90 years of age will experience hip

fracture. Mortality with hip fracture higher in men than fracture. Mortality with hip fracture higher in men than in women.in women.

--Treatment includes testosterone therapy (unless --Treatment includes testosterone therapy (unless contraindicated—see question) as first line, as well as contraindicated—see question) as first line, as well as bisphonate therapy (works equally well in men—see bisphonate therapy (works equally well in men—see question). Likely role for recombinant PTH and possibly question). Likely role for recombinant PTH and possibly SERMs (raloxifene). SERMs (raloxifene).

--Must assure adequate calcium and vitamin D intake, --Must assure adequate calcium and vitamin D intake, although these are not sufficient for treatment of although these are not sufficient for treatment of osteoporosisosteoporosis

--Diagnosis best made with DEXA, still compared to --Diagnosis best made with DEXA, still compared to standard of young womanstandard of young woman

What they want you to What they want you to know…know…

A 79-year old white male with a previous history of prostate A 79-year old white male with a previous history of prostate cancer has a lumbar spine film suggesting osteopenia. cancer has a lumbar spine film suggesting osteopenia. Subsequent bone density studies show a T score of -2.7. Subsequent bone density studies show a T score of -2.7. Which one of the following is appropriate first line therapy Which one of the following is appropriate first line therapy for this patient?for this patient?

A) TestosteroneA) Testosterone B) Calcitonin nasal spray (Micalcin)B) Calcitonin nasal spray (Micalcin) C) Raloxifene (Evista)C) Raloxifene (Evista) D) Alendronate (Fosamax)D) Alendronate (Fosamax)

Which one of the following is true regarding the use of Which one of the following is true regarding the use of Alendronate (Fosamax) for the treatment of osteoporosis in Alendronate (Fosamax) for the treatment of osteoporosis in men?men?

A)A) Its effectiveness is similar to that seen in womenIts effectiveness is similar to that seen in women B) It is ineffective in patients with Paget’s diseaseB) It is ineffective in patients with Paget’s disease C) It is contraindicated in patients taking NSAIDsC) It is contraindicated in patients taking NSAIDs D) It causes a decrease in heightD) It causes a decrease in height

Chronic ManagementChronic Management --No advantage of remeasuring BMD within 1 --No advantage of remeasuring BMD within 1

yearyear --Recommendations for remeasurement in 1 or 2 --Recommendations for remeasurement in 1 or 2

years once therapy has been startedyears once therapy has been started --If evaluated, and no change at one year, not --If evaluated, and no change at one year, not

indicative of eventual benefit. Recommend indicative of eventual benefit. Recommend ensuring adequate calcium Vit D, and additional ensuring adequate calcium Vit D, and additional risk factor reduction (smoking cessation, risk factor reduction (smoking cessation, deacreased EtOH, etc.)If significant worsening, deacreased EtOH, etc.)If significant worsening, likely unresponsive to therapy. If improvement, likely unresponsive to therapy. If improvement, continue regimen and follow long term. continue regimen and follow long term.

What they want you to What they want you to know…know…

A 70-year-old female had a lumbar vertebral fracture A 70-year-old female had a lumbar vertebral fracture 3 years ago. At that time she had a dual-energy 3 years ago. At that time she had a dual-energy absorptiometry (DEXA) scan, with a T score of -2.6, absorptiometry (DEXA) scan, with a T score of -2.6, and was placed on alendronate (Fosamax), calcium, and was placed on alendronate (Fosamax), calcium, and vitamin D. She recently quit smoking. Her BMI and vitamin D. She recently quit smoking. Her BMI is 21. A DEXA scan today shows her bone mineral is 21. A DEXA scan today shows her bone mineral density to be -2.1. density to be -2.1.

Which one of the following would be most Which one of the following would be most appropriate in the management of this patient?appropriate in the management of this patient?

Replace alendronate with raloxifene (Evista)Replace alendronate with raloxifene (Evista) Stop alendronate, but continue calcium and vitamin DStop alendronate, but continue calcium and vitamin D Add raloxifene to her regimenAdd raloxifene to her regimen Add teriparatide (Forteo) to her regimenAdd teriparatide (Forteo) to her regimen Make no change to her regimenMake no change to her regimen

FallsFalls --Fracture risk is still significantly linked to risk of --Fracture risk is still significantly linked to risk of

fall fall --Ability to safely transfer is independent risk factor--Ability to safely transfer is independent risk factor --Vitamin D has been shown in numerous studies to --Vitamin D has been shown in numerous studies to

decrease risk of falls independent of the structural decrease risk of falls independent of the structural bone benefitbone benefit

What they want you to What they want you to know…know…

Which one of the following has been Which one of the following has been shown to reduce the risk of falls in shown to reduce the risk of falls in the elderly?the elderly?

Vitamin DVitamin D Amityriptyline (Elavil)Amityriptyline (Elavil) Haloperidol (Haldol)Haloperidol (Haldol) Lorazepam (Ativan)Lorazepam (Ativan)

Acute ComplicationsAcute Complications Remember that Calcitonin has additional benefit of pain Remember that Calcitonin has additional benefit of pain

reduction in acute course of compression fracturereduction in acute course of compression fracture

A 70-year-old white female with osteoporosis sees you for A 70-year-old white female with osteoporosis sees you for follow-up a few days after an emergency follow-up a few days after an emergency room visit for an acute T12 vertebral compression fractureroom visit for an acute T12 vertebral compression fracture . The fracture was suspected . The fracture was suspected clinically and on plain films; the diagnosis was confirmed with a bone scan. The emergency department physician prescribed oxycontin and NSAIDs, clinically and on plain films; the diagnosis was confirmed with a bone scan. The emergency department physician prescribed oxycontin and NSAIDs, but the patient is still experiencing considerable discomfort. but the patient is still experiencing considerable discomfort.

In addition to increasing the dosage of oxycodone, which one of the following interventions would you suggest now to reduce the patient’s pain?In addition to increasing the dosage of oxycodone, which one of the following interventions would you suggest now to reduce the patient’s pain?

Calcitonin (Miacalcin)Calcitonin (Miacalcin) Raloxifene (Evista)Raloxifene (Evista) Alendronate (Fosamax)Alendronate (Fosamax) Physical therapy, including dexamethasone iontophoresisPhysical therapy, including dexamethasone iontophoresis VertebroplastyVertebroplasty

A 78-year-old white female presents with a 3-day history of lower thoracic back pain. She denies any antecedent fall or trauma, and first noted pain A 78-year-old white female presents with a 3-day history of lower thoracic back pain. She denies any antecedent fall or trauma, and first noted pain upon arising. Her description of the pain indicates that it is severe, bilateral, and without radiation to the arms or legs. upon arising. Her description of the pain indicates that it is severe, bilateral, and without radiation to the arms or legs.

Her past medical history is positive for hypertension and controlled diabetes milletus. Her meds include HCTZ, enalipril, metformin, and MVI. She Her past medical history is positive for hypertension and controlled diabetes milletus. Her meds include HCTZ, enalipril, metformin, and MVI. She is a previous smoker but does not drink alcohol. She underwent menopause at age 50 and took estrogen for a few months for hot flashes. Physical is a previous smoker but does not drink alcohol. She underwent menopause at age 50 and took estrogen for a few months for hot flashes. Physical exam reveals her to be in moderate pain with a somewhat stooped posture and mild tenderness over T12-L1. She has negative straight leg raising exam reveals her to be in moderate pain with a somewhat stooped posture and mild tenderness over T12-L1. She has negative straight leg raising and normal lower extremity sensation, strength, and reflexes.and normal lower extremity sensation, strength, and reflexes.

Which of the following is true regarding this patient’s likely condition?Which of the following is true regarding this patient’s likely condition? An MRI or nuclear medicine bone scan should be performedAn MRI or nuclear medicine bone scan should be performed Prolonged (approximately 2 weeks) bed rest will increase the chance of complete recoveryProlonged (approximately 2 weeks) bed rest will increase the chance of complete recovery Investigation for an underlying malignancy is indicatedInvestigation for an underlying malignancy is indicated

Subcutaneous or intranasal calcitonin (Calcimar, Subcutaneous or intranasal calcitonin (Calcimar, Miacalcin) may be very helpful for pain reliefMiacalcin) may be very helpful for pain relief

Questions?Questions?