A SILENT KILLERA SILENT KILLER

NADIA MALIK, MDNADIA MALIK, MD

NUCLEAR MEDICINENUCLEAR MEDICINE

KAISER PERMANENTEKAISER PERMANENTE

NAPA SALANO REGION, CANAPA SALANO REGION, CA

DEFINITION DEFINITION

It is characterized by low bone It is characterized by low bone mass, deterioration of bone tissue mass, deterioration of bone tissue and disruption of bone architecture, and disruption of bone architecture, compromised bone strength and an compromised bone strength and an increase in the risk of fracture.increase in the risk of fracture.

MEDLINE: Osteoporosis is the MEDLINE: Osteoporosis is the thinning of bone tissue and loss of thinning of bone tissue and loss of bone density over time.bone density over time.

COMPARISON OF NORMAL AND COMPARISON OF NORMAL AND OSTEOPOROTIC BONEOSTEOPOROTIC BONE changes within cancellous bone as a consequence of bone loss. changes within cancellous bone as a consequence of bone loss. Individual trabecular plates of bone are lost, leaving an Individual trabecular plates of bone are lost, leaving an architecturally weakened structure with significantly reduced mass.architecturally weakened structure with significantly reduced mass.

SCOPE OF THE SCOPE OF THE PROBLEMPROBLEM Based on data from NHANES III survey, NOF has Based on data from NHANES III survey, NOF has

estimated:estimated: 10 million Americans have osteoporosis10 million Americans have osteoporosis 33.6 million have low bone density of the hip. 33.6 million have low bone density of the hip. About 1 in 2 Caucasian women will experience About 1 in 2 Caucasian women will experience

an osteoporosis-related fracture at some point an osteoporosis-related fracture at some point in her lifetime, as will 1 in 5 men. in her lifetime, as will 1 in 5 men.

AA females with osteoporosis have the same AA females with osteoporosis have the same elevated fracture risk as Caucasianselevated fracture risk as Caucasians. .

MEDICAL IMPACT MEDICAL IMPACT Fractures and their complications are the relevant clinical sequelae of Fractures and their complications are the relevant clinical sequelae of

osteoporosis. The most common fractures are those of the vertebrae (spine), osteoporosis. The most common fractures are those of the vertebrae (spine), proximal femur (hip) and distal forearm (wrist). Fractures may be followed by full proximal femur (hip) and distal forearm (wrist). Fractures may be followed by full recovery or by chronic pain, disability and death. recovery or by chronic pain, disability and death.

These fractures can cause psychological symptoms, depression, loss of self-These fractures can cause psychological symptoms, depression, loss of self-esteem, physical limitations, lifestyle and cosmetic changes. Anxiety, fear and esteem, physical limitations, lifestyle and cosmetic changes. Anxiety, fear and anger. anger.

The high morbidity and consequent dependency associated with these fractures The high morbidity and consequent dependency associated with these fractures strain interpersonal relationships and social roles for patients and their families. strain interpersonal relationships and social roles for patients and their families.

Hip fractures result in 10 to 20% excess mortality within one year. Hip fractures result in 10 to 20% excess mortality within one year. Hip fractures are associated with a 2.5 fold increased risk of future fractures. Hip fractures are associated with a 2.5 fold increased risk of future fractures. Approximately 20% of hip fracture patients require long-term nursing home care, Approximately 20% of hip fracture patients require long-term nursing home care,

and 40% fully regain their pre-fracture level of independence.and 40% fully regain their pre-fracture level of independence. Mortality is also increased following vertebral fractures, complications include Mortality is also increased following vertebral fractures, complications include

back pain, height loss and postural changes associated with kyphosis limit back pain, height loss and postural changes associated with kyphosis limit activity. activity.

Multiple thoracic fractures may result in restrictive lung disease. Lumbar Multiple thoracic fractures may result in restrictive lung disease. Lumbar fractures may alter abdominal anatomy, leading to constipation, abdominal pain, fractures may alter abdominal anatomy, leading to constipation, abdominal pain, distention, reduced appetite and premature satiety. distention, reduced appetite and premature satiety.

FINANCIAL IMPACTFINANCIAL IMPACT Osteoporosis-related fractures create a heavy economic Osteoporosis-related fractures create a heavy economic

burden, causing more than 432,000 hospital admissions, burden, causing more than 432,000 hospital admissions, Almost 2.5 million medical office visits Almost 2.5 million medical office visits About 180,000 nursing home admissions annually in the About 180,000 nursing home admissions annually in the

US.US. The cost to the healthcare system associated with The cost to the healthcare system associated with

osteoporosis-related fractures has been estimated at $17 osteoporosis-related fractures has been estimated at $17 billion for 2005.billion for 2005.

Hip fractures account for 14% of incidental fractures, 72% of Hip fractures account for 14% of incidental fractures, 72% of fracture costs.fracture costs.

Due to the aging population, the Surgeon General estimates Due to the aging population, the Surgeon General estimates that the number of hip fractures and their associated that the number of hip fractures and their associated complications could significantly increase by 2040.complications could significantly increase by 2040.

Factors that cause or Factors that cause or contribute to osteoporosiscontribute to osteoporosis Low Calcium intakeLow Calcium intake Vitamin D deficiencyVitamin D deficiency Excess Vitamin AExcess Vitamin A High Caffeine intakeHigh Caffeine intake High Salt intake High Salt intake Aluminum in antacidsAluminum in antacids Alcohol- 3 or more drinks/dayAlcohol- 3 or more drinks/day Inadequate physical activityInadequate physical activity ImmobilizationImmobilization Smoking passive or activeSmoking passive or active Frequent fallingFrequent falling Having a fracture after age 50Having a fracture after age 50 A parent or a sibling who has had a hip A parent or a sibling who has had a hip

fracturefracture Low BMI <21, weighing <127 lbsLow BMI <21, weighing <127 lbs

Medical risk factorsMedical risk factors   AgeAge Anxiety and agitationAnxiety and agitation ArrhythmiasArrhythmias DehydrationDehydration DepressionDepression Female genderFemale gender Impaired transfer and mobility Impaired transfer and mobility  Poor vision and use of bifocals Poor vision and use of bifocals Reduced mental acuity and diminished Reduced mental acuity and diminished

cognitive skills cognitive skills Urgent urinary incontinence Urgent urinary incontinence Vitamin D insufficiency Vitamin D insufficiency

Genetic factors:Genetic factors:

   Cystic FibrosisCystic Fibrosis HomocystinuriaHomocystinuria Osteogenesis ImperfectaOsteogenesis Imperfecta

Hypgonadal States: Hypgonadal States:

Anorexia nervosa and bulimia Anorexia nervosa and bulimia Athletic amenorrhea Athletic amenorrhea Premature Ovarian FailurePremature Ovarian Failure

Endocrine disorders: Endocrine disorders: Diabetes MellitusDiabetes Mellitus Adrenal insufficiency Adrenal insufficiency Cushing’s syndrome Cushing’s syndrome ThyrotoxicosisThyrotoxicosis HyperparathyroidismHyperparathyroidism

  

Gastrointestinal disorders Gastrointestinal disorders Celiac disease Celiac disease Inflammatory bowel disease Inflammatory bowel disease Gastric bypass Gastric bypass GI surgery GI surgery MalabsorptionMalabsorption Pancreatic diseasePancreatic disease

  

Hematologic disorders Hematologic disorders Hemophilia Hemophilia Leukemia and Leukemia and lymphomas lymphomas Multiple myeloma Multiple myeloma Sickle cell disease Sickle cell disease Thalassemia Thalassemia

Rheumatic and autoimmune Rheumatic and autoimmune diseases diseases Ankylosing spondylitis Ankylosing spondylitis Lupus (SLE)Lupus (SLE) Rheumatoid arthritis Rheumatoid arthritis

Miscellaneous conditions and Miscellaneous conditions and diseases diseases Alcoholism Alcoholism Emphysema Emphysema Muscular dystrophy Muscular dystrophy Amyloidosis Amyloidosis End stage renal disease End stage renal disease Parenteral nutrition Parenteral nutrition Chronic metabolic acidosis Chronic metabolic acidosis Epilepsy Epilepsy Post-transplant bone disease Post-transplant bone disease Congestive heart failure Congestive heart failure Idiopathic scoliosis Idiopathic scoliosis Prior fracture as an adult Prior fracture as an adult Depression Depression Multiple sclerosis Multiple sclerosis Sarcoidosis Sarcoidosis

  MedicationsMedications

Anticoagulants (heparin) Anticoagulants (heparin) Cancer chemotherapeutic drugs Cancer chemotherapeutic drugs AnticonvulsantsAnticonvulsants Cyclosporine A and tacrolimusCyclosporine A and tacrolimus LithiumLithium Aromatase inhibitorsAromatase inhibitors Depo-medroxyprogesteroneDepo-medroxyprogesterone BarbituratesBarbiturates Glucocorticoids (≥ 5 mg/d of Glucocorticoids (≥ 5 mg/d of

prednisone or equivalent for ≥ 3 mo) prednisone or equivalent for ≥ 3 mo)

Environmental risk factorsEnvironmental risk factors Lack of assistive devices in Lack of assistive devices in

bathroomsbathrooms Loose throw rugsLoose throw rugs Low level lightingLow level lighting Obstacles in the walking path Obstacles in the walking path Slippery outdoor conditions Slippery outdoor conditions

DIAGNOSISDIAGNOSIS

TOP: NORMAL TOP: NORMAL BONEBONE

BOTTOM: BOTTOM: OSTEOPOROTIC OSTEOPOROTIC BONEBONE

DIAGNOSISDIAGNOSIS

BMD can be measured by a BMD can be measured by a DEXA SCAN, which is the gold DEXA SCAN, which is the gold standard for the diagnosis of standard for the diagnosis of osteoporosis. osteoporosis.

A clinical diagnosis can often A clinical diagnosis can often be made in at-risk individuals be made in at-risk individuals who sustain a low-trauma who sustain a low-trauma fracture.fracture.

Indications for BMD Testing: Indications for BMD Testing:

Women age 65 and older and men age 70 Women age 65 and older and men age 70 and older, regardless of clinical risk factors and older, regardless of clinical risk factors

Younger postmenopausal women and men Younger postmenopausal women and men age 50 to 69 with compromised bone density age 50 to 69 with compromised bone density risk factors risk factors

Peri menopausal women with specific risk Peri menopausal women with specific risk factors associated with increased fracture factors associated with increased fracture risk such as low body weight, prior low-risk such as low body weight, prior low-trauma fracture or high risk medication trauma fracture or high risk medication

Adults who have a fracture after age 50 Adults who have a fracture after age 50 Adults with a condition (e.g., rheumatoid Adults with a condition (e.g., rheumatoid

arthritis) or taking a medication (e.g., arthritis) or taking a medication (e.g., glucocorticoids in a daily dose ≥ 5 mg glucocorticoids in a daily dose ≥ 5 mg prednisone or equivalent for ≥ three months) prednisone or equivalent for ≥ three months) associated with low bone mass or bone loss associated with low bone mass or bone loss

CONT’DCONT’D Anyone being considered for pharmacologic Anyone being considered for pharmacologic

therapy for osteoporosis therapy for osteoporosis Anyone being treated for osteoporosis, to Anyone being treated for osteoporosis, to

monitor treatment effect monitor treatment effect

Anyone not receiving therapy in whom Anyone not receiving therapy in whom evidence of bone loss would lead to evidence of bone loss would lead to treatmenttreatment

Postmenopausal women discontinuing Postmenopausal women discontinuing estrogen should be considered for bone estrogen should be considered for bone density testingdensity testing

BMD testing for many individuals BMD testing for many individuals age 65 and younger, including but age 65 and younger, including but not limited to:not limited to:

Estrogen deficient women at clinical risk for Estrogen deficient women at clinical risk for osteoporosis osteoporosis

Individuals with vertebral abnormalities Individuals with vertebral abnormalities Individuals receiving, or planning to receive, Individuals receiving, or planning to receive,

long-term glucocorticoid therapy in a daily long-term glucocorticoid therapy in a daily dose ≥ 5 mg prednisone or equivalent for ≥ dose ≥ 5 mg prednisone or equivalent for ≥ three monthsthree months

Individuals with primary hyperparathyroidism Individuals with primary hyperparathyroidism Individuals being monitored to assess the Individuals being monitored to assess the

response or efficacy of an approved response or efficacy of an approved osteoporosis drug therapy osteoporosis drug therapy

  

Bone Mineral Density Bone Mineral Density Measurement and Measurement and ClassificationClassification Dual-energy x-ray absorptiometry Dual-energy x-ray absorptiometry

(DXA) measurement of the hip (DXA) measurement of the hip and spine is the technology now and spine is the technology now used to establish or confirm a used to establish or confirm a diagnosis of osteoporosis, predict diagnosis of osteoporosis, predict future fracture risk and monitor future fracture risk and monitor patients by performing serial patients by performing serial assessments assessments

TABLE:TABLE:

Defining Osteoporosis by BMD Defining Osteoporosis by BMD Normal: Normal: BMD is within 1 SD of a “young normal” BMD is within 1 SD of a “young normal”

adult (T-score at -1.0 and above). adult (T-score at -1.0 and above). Low bone mass (“osteopenia”): Low bone mass (“osteopenia”): BMD is BMD is

between 1.0 and 2.5 SD below that of a “young between 1.0 and 2.5 SD below that of a “young normal” adult (T-score between -1.0 and -2.5). normal” adult (T-score between -1.0 and -2.5).

Osteoporosis: Osteoporosis: BMD is 2.5 SD or more below that BMD is 2.5 SD or more below that of a “young normal” adult (T-score at or below of a “young normal” adult (T-score at or below -2.5). Patients in this group who have already -2.5). Patients in this group who have already experienced one or more fractures are deemed experienced one or more fractures are deemed to have severe or “established” osteoporosis. to have severe or “established” osteoporosis.

*↑Risk of fracture by 1.5-3.0 x for each SD *↑Risk of fracture by 1.5-3.0 x for each SD decreasedecrease

Z- and T-Scores:Z- and T-Scores: From: ISCD Bone Densitometry Clinician Course. Lecture 5 (2008).From: ISCD Bone Densitometry Clinician Course. Lecture 5 (2008).

DIAGNOSIS: CONT’DDIAGNOSIS: CONT’D

.. In postmenopausal women and men age 50 In postmenopausal women and men age 50 years and older, the WHO diagnostic T-score years and older, the WHO diagnostic T-score criteria (normal, low bone mass and criteria (normal, low bone mass and osteoporosis) are applied to BMD osteoporosis) are applied to BMD measurement by central DXA at the lumbar measurement by central DXA at the lumbar spine and femoral neck.spine and femoral neck.

.. BMD measured by DXA at the one-third (33 BMD measured by DXA at the one-third (33 %) radius site can be used for diagnosing %) radius site can be used for diagnosing osteoporosis when the hip and spine cannot osteoporosis when the hip and spine cannot be measured. be measured.

DIAGNOSISDIAGNOSIS

In premenopausal women, men less than In premenopausal women, men less than 50 years of age and children, the WHO 50 years of age and children, the WHO BMD diagnostic classification should not BMD diagnostic classification should not be applied. tbe applied. the diagnosis of osteoporosis he diagnosis of osteoporosis should not be made on the basis of should not be made on the basis of densitometric criteria alone. The (ISCD) densitometric criteria alone. The (ISCD) recommends that instead of T-scores, ethnic recommends that instead of T-scores, ethnic or race adjusted Z-scores should be used, with or race adjusted Z-scores should be used, with Z-scores of -2.0 or lower defined as either “low Z-scores of -2.0 or lower defined as either “low bone mineral density for chronological age” or bone mineral density for chronological age” or “below the expected range for age” and those “below the expected range for age” and those above -2.0 being “within the expected range above -2.0 being “within the expected range for age.”for age.”

OTHER DIAGNOSTIC OTHER DIAGNOSTIC MODALITIESMODALITIES

Peripheral dual-energy x-ray Peripheral dual-energy x-ray absorptiometry (pDXA) absorptiometry (pDXA) measures real measures real bone density of the forearm, finger or heel. bone density of the forearm, finger or heel. Measurement by validated pDXA devices can Measurement by validated pDXA devices can be used to assess vertebral and overall be used to assess vertebral and overall fracture risk in postmenopausal women. fracture risk in postmenopausal women. There is lack of sufficient evidence for There is lack of sufficient evidence for fracture prediction in men. pDXA is fracture prediction in men. pDXA is associated with exposure to trivial amounts associated with exposure to trivial amounts of radiation. pDXA is not appropriate for of radiation. pDXA is not appropriate for monitoring BMD after treatment. monitoring BMD after treatment.

CT BASED CT BASED ABSORPTIOMETRYABSORPTIOMETRY

CT-based absorptiometry. Quantitative CT-based absorptiometry. Quantitative computed tomography (QCT) computed tomography (QCT) measures volumetric measures volumetric trabecular and cortical bone density at the spine and trabecular and cortical bone density at the spine and hip, whereas hip, whereas peripheral QCT (pQCT) peripheral QCT (pQCT) measures the measures the same at the forearm or tibia. In postmenopausal same at the forearm or tibia. In postmenopausal women, QCT measurement of spine trabecular BMD women, QCT measurement of spine trabecular BMD can predict vertebral fractures whereas pQCT of the can predict vertebral fractures whereas pQCT of the forearm at the ultra distal radius predicts hip, but not forearm at the ultra distal radius predicts hip, but not vertebral fractures. There is lack of sufficient evidence vertebral fractures. There is lack of sufficient evidence for fracture prediction in men. QCT and pQCT are for fracture prediction in men. QCT and pQCT are associated with greater amounts of radiation exposure associated with greater amounts of radiation exposure than central DXA or pDXA. than central DXA or pDXA.

US DENSITOMETRYUS DENSITOMETRY

Quantitative ultrasound densitometry Quantitative ultrasound densitometry (QUS) (QUS) does not measure BMD directly but does not measure BMD directly but rather speed of sound (SOS) and/or broadband rather speed of sound (SOS) and/or broadband ultrasound attenuation (BUA) at the heel, tibia, ultrasound attenuation (BUA) at the heel, tibia, patella and other peripheral skeletal sites. A patella and other peripheral skeletal sites. A composite parameter using SOS and BUA may composite parameter using SOS and BUA may be used clinically. Validated heel QUS devices be used clinically. Validated heel QUS devices predict fractures in postmenopausal women predict fractures in postmenopausal women (vertebral, hip and overall fracture risk) and in (vertebral, hip and overall fracture risk) and in men 65 and older (hip and non-vertebral men 65 and older (hip and non-vertebral fractures). QUS is not associated with any fractures). QUS is not associated with any radiation exposure. radiation exposure.

UNIVERSAL RECOMMENDATIONSUNIVERSAL RECOMMENDATIONS FOR PREVENTION FOR PREVENTION AND CONTROL OF LOW BMD AND CONTROL OF LOW BMD

ADEQUATE INTAKE OF CALCIUM ADEQUATE INTAKE OF CALCIUM NOF’s Calcium RecommendationsNOF’s Calcium Recommendations

Adults under age 50 Adults under age 50 need 1,000 mg of need 1,000 mg of calcium every daycalcium every day

Adults age 50 and older Adults age 50 and older need 1,200 mg of need 1,200 mg of calcium calcium

every dayevery day

Estimating Daily Dietary Calcium IntakeEstimating Daily Dietary Calcium Intake

STEP 1: Estimate calcium intake from calcium-rich STEP 1: Estimate calcium intake from calcium-rich foods*foods*

Product Servings/d Estimated calcium/serving(mg) Product Servings/d Estimated calcium/serving(mg) Calcium(mg) Calcium(mg)

Milk (8 oz.) ________ x 300 = Milk (8 oz.) ________ x 300 = __________________

Yogurt (6 oz.) ________ x 300 = Yogurt (6 oz.) ________ x 300 = _________ _________

Cheese (1 oz/ 1 cubic in.)________ x 200 = Cheese (1 oz/ 1 cubic in.)________ x 200 = __________ __________

Fortified foods or juices ________ x80 to 1,000** = Fortified foods or juices ________ x80 to 1,000** = __________ __________

STEP 2:STEP 2: Total from above + 250 mg for nondairy sources Total from above + 250 mg for nondairy sources= total dietary calcium Calcium (mg) = total dietary calcium Calcium (mg)

* About 75 to 80 percent of the calcium consumed in American diets is from dairy products.* About 75 to 80 percent of the calcium consumed in American diets is from dairy products. ** Calcium content of fortified foods varies.** Calcium content of fortified foods varies.

ADEQUATE INTAKE OF VITAMIN ADEQUATE INTAKE OF VITAMIN DD

NOF’s Vitamin D RecommendationsNOF’s Vitamin D Recommendations Vitamin D plays a major role in calcium Vitamin D plays a major role in calcium

absorption, bone health, muscle absorption, bone health, muscle performance, balance and risk of performance, balance and risk of falling.falling.

Adults under age 50 Adults under age 50 need 400–800 need 400–800 IU of vitamin D every dayIU of vitamin D every day

Adults age 50 and older Adults age 50 and older need 800-need 800-1,000 IU of vitamin D every day1,000 IU of vitamin D every day

Chief dietary sources Chief dietary sources of Vitamin Dof Vitamin D

. Vitamin D-fortified milk (soy milk may . Vitamin D-fortified milk (soy milk may not be supplemented with vitamin D)not be supplemented with vitamin D)

. Cereals (40 to 50 IU per serving) . Cereals (40 to 50 IU per serving)

. Egg yolks . Egg yolks

. Salt-water fish . Salt-water fish

. Liver . Liver

. Calcium supplements . Calcium supplements

most multivitamin tablets. most multivitamin tablets.

Vitamin D Vitamin D

Serum 25(OH)D levels should be measured in Serum 25(OH)D levels should be measured in elderly patients at high risk for vitamin D elderly patients at high risk for vitamin D deficiency, including patients with deficiency, including patients with malabsorption (e.g., celiac disease) and malabsorption (e.g., celiac disease) and chronic renal insufficiency, housebound chronic renal insufficiency, housebound patients, chronically ill patients and others patients, chronically ill patients and others with with limited sun exposurelimited sun exposure will need more. will need more. vitamin D should be supplemented in vitamin D should be supplemented in amounts sufficient to bring the serum amounts sufficient to bring the serum 25(OH)D level to 30 ng/ml (75 nmol/L) or 25(OH)D level to 30 ng/ml (75 nmol/L) or higher. The safe upper limit for vitamin D higher. The safe upper limit for vitamin D intake for the general adult population was intake for the general adult population was set at 2,000 IU per day in 1997.set at 2,000 IU per day in 1997.

healthy and well-healthy and well-balanced dietbalanced diet

A well-balanced diet that includes fruits A well-balanced diet that includes fruits and vegetables is also good for your and vegetables is also good for your bones. But, very high amounts of bones. But, very high amounts of protein, salt (sodium) or caffeine can protein, salt (sodium) or caffeine can cause bone loss. You can help prevent cause bone loss. You can help prevent some of this loss by getting the amount some of this loss by getting the amount of calcium your body needs. While of calcium your body needs. While extremely high protein diets can cause extremely high protein diets can cause bone loss, it is still important to eat abone loss, it is still important to eat a

well-balanced diet that contains protein. well-balanced diet that contains protein.

Exercise at least 2½ hrs Exercise at least 2½ hrs every weekevery week

Weight-bearing and muscle-strengthening Weight-bearing and muscle-strengthening exercises help keep your bones strong exercises help keep your bones strong and healthy. Some examples of weight-and healthy. Some examples of weight-bearing exercises are dancing, jogging, bearing exercises are dancing, jogging, elliptical training machines, aerobics and elliptical training machines, aerobics and brisk walking. Some examples of muscle brisk walking. Some examples of muscle strengthening exercises are lifting strengthening exercises are lifting weights, using elastic exercise bands, weights, using elastic exercise bands, lifting your own body weight or using lifting your own body weight or using weight machines. If you have weight machines. If you have osteoporosis, check with your healthcare osteoporosis, check with your healthcare provider before beginning a new training provider before beginning a new training program.program.

Don’t smoke or drink too Don’t smoke or drink too much alcoholmuch alcohol

Smoking and drinking three Smoking and drinking three or more alcoholic drinks a or more alcoholic drinks a day are bad for your bones.day are bad for your bones.

See your healthcare See your healthcare provider every year.provider every year.

Schedule an appointment Schedule an appointment with your doctor or other with your doctor or other healthcare provider at least healthcare provider at least once a year. Make your once a year. Make your healthcare provider your healthcare provider your partner in keeping your partner in keeping your bones healthy.bones healthy.

FALL PREVENTIONFALL PREVENTION

In addition to maintaining adequate In addition to maintaining adequate vitamin D levels and physical activity, vitamin D levels and physical activity, strategies to reduce falls should be strategies to reduce falls should be assessed. These include, but are not assessed. These include, but are not limited to, checking and correcting vision limited to, checking and correcting vision and hearing, evaluating any neurological and hearing, evaluating any neurological problems, reviewing prescription problems, reviewing prescription medications for side effects that may medications for side effects that may affect balance and providing a checklist affect balance and providing a checklist for improving safety at home. for improving safety at home.

USE OF WHO FRACTURE RISK ALGORITHM (FRAX®) IN THE USE OF WHO FRACTURE RISK ALGORITHM (FRAX®) IN THE USUS

FRAX® was developed to calculate the 10-FRAX® was developed to calculate the 10-year probability of a hip fracture and of a year probability of a hip fracture and of a major osteoporotic fracture (defined as major osteoporotic fracture (defined as clinical vertebral, hip, forearm or proximal clinical vertebral, hip, forearm or proximal humerus fracture) taking into account femoral humerus fracture) taking into account femoral neck BMD and the clinical risk factors. The neck BMD and the clinical risk factors. The WHO algorithm used in this Guide was WHO algorithm used in this Guide was calibrated to US fracture and mortality rates. calibrated to US fracture and mortality rates. It is cost-effective to treat individuals with a It is cost-effective to treat individuals with a prior hip or vertebral fracture and those with prior hip or vertebral fracture and those with a DXA femoral neck T-score ≤ -2.5. Previous a DXA femoral neck T-score ≤ -2.5. Previous analyses have established that a spine T-analyses have established that a spine T-score ≤ -2.5 also warrants treatment. FRAX® score ≤ -2.5 also warrants treatment. FRAX® is most useful in patients with low hip BMD. is most useful in patients with low hip BMD.

WHO SHOULD BE CONSIDERED FOR WHO SHOULD BE CONSIDERED FOR TREATMENT?TREATMENT?

Postmenopausal women and men age 50 and older Postmenopausal women and men age 50 and older presenting with the following should be considered for presenting with the following should be considered for treatment: treatment: – A hip or vertebral (clinical or morphometric) A hip or vertebral (clinical or morphometric)

fracturefracture– T-score ≤ -2.5 at the femoral neck or spine after T-score ≤ -2.5 at the femoral neck or spine after

appropriate evaluation to exclude secondary appropriate evaluation to exclude secondary causescauses

Low bone mass (T-score between -1.0 and -2.5 at the Low bone mass (T-score between -1.0 and -2.5 at the femoral neck or spine) and a 10-year probability of a femoral neck or spine) and a 10-year probability of a hip fracture ≥ 3% or a 10-year probability of a major hip fracture ≥ 3% or a 10-year probability of a major osteoporosis-related fracture ≥ 20% based on the US-osteoporosis-related fracture ≥ 20% based on the US-adapted WHO algorithmadapted WHO algorithm

FDA-approved pharmacologic options for the FDA-approved pharmacologic options for the prevention and/or treatment of postmenopausal prevention and/or treatment of postmenopausal osteoporosis osteoporosis

.. BisphosphonatesBisphosphonates (alendronate, alendronate (alendronate, alendronate plus D, ibandronate, risedronate, risedronate with plus D, ibandronate, risedronate, risedronate with 500 mg of calcium carbonate and zoledronic acid), 500 mg of calcium carbonate and zoledronic acid),

.. CalcitoninCalcitonin

.. EstrogensEstrogens (estrogen and/or hormone therapy), (estrogen and/or hormone therapy),

.. Estrogen agonist/antagonistEstrogen agonist/antagonist (raloxifene) and (raloxifene) and

.. Parathyroid hormoneParathyroid hormone [PTH(1-34), teriparatide]. [PTH(1-34), teriparatide].

Bisphosphonates: Bisphosphonates: Derivatives of inorganic Derivatives of inorganic pyrophosphate (PPi), a naturally occurring compound in pyrophosphate (PPi), a naturally occurring compound in the body.the body.

Actonel(risedronate), daily or weeklyActonel(risedronate), daily or weekly Fosamax(alendronate) daily or weeklyFosamax(alendronate) daily or weekly Boniva (Ibandronate), oral or IV, daily or Boniva (Ibandronate), oral or IV, daily or

monthlymonthly Work by inhibiting osteoclast function. They Work by inhibiting osteoclast function. They

inhibit mineralization of the bones (which inhibit mineralization of the bones (which makes them stronger) and they also inhibit makes them stronger) and they also inhibit bone breakdown.bone breakdown.

Side effects and administration of Side effects and administration of bisphosphonates.bisphosphonates.

Side effects are similar for all oral Side effects are similar for all oral bisphosphonate medications and include bisphosphonate medications and include gastrointestinal problems such as difficulty gastrointestinal problems such as difficulty swallowing, inflammation of the esophagus swallowing, inflammation of the esophagus and gastric ulcer. There have been reports of and gastric ulcer. There have been reports of osteonecrosis of the jaw (particularly osteonecrosis of the jaw (particularly following intravenous bisphosphonate following intravenous bisphosphonate treatment for patients with cancer) and of treatment for patients with cancer) and of visual disturbances. The level of risk is not visual disturbances. The level of risk is not known, but appears extremely small for at known, but appears extremely small for at least up to five years. There was a higher risk least up to five years. There was a higher risk of developing atrial fibrillation for patients on of developing atrial fibrillation for patients on zoledronic acid. zoledronic acid.

CalcitoninCalcitonin

Brand name: Miacalcin® or Fortical®. Brand name: Miacalcin® or Fortical®. Salmon calcitonin is FDA-approved for the Salmon calcitonin is FDA-approved for the treatment of osteoporosis in women who are treatment of osteoporosis in women who are at least five years postmenopausal. It is at least five years postmenopausal. It is delivered as a single daily intranasal spray delivered as a single daily intranasal spray that provides 200 IU of the drug or sub/q that provides 200 IU of the drug or sub/q administration also is available. Intranasal administration also is available. Intranasal calcitonin is generally considered safe calcitonin is generally considered safe although some patients experience rhinitis although some patients experience rhinitis and, rarely, epistaxis. and, rarely, epistaxis.

Estrogen/Hormone Therapy (ET/HT)Estrogen/Hormone Therapy (ET/HT)

Estrogen/hormone therapy is approved by the FDA for the Estrogen/hormone therapy is approved by the FDA for the prevention of OP, relief of vasomotor and other symptoms prevention of OP, relief of vasomotor and other symptoms associated with menopause. Women who have not had a associated with menopause. Women who have not had a hysterectomy require HT, which contains progestin to protect hysterectomy require HT, which contains progestin to protect the uterine lining. The Woman’s Health Initiative (WHI) found the uterine lining. The Woman’s Health Initiative (WHI) found that 5 years of HT (Prempro®) reduced the risk of clinical that 5 years of HT (Prempro®) reduced the risk of clinical vertebral fractures and hip fractures by 34% and other vertebral fractures and hip fractures by 34% and other osteoporotic fractures by 23%. osteoporotic fractures by 23%.

The WHI reported increased risks of MI, stroke, invasive breast The WHI reported increased risks of MI, stroke, invasive breast Ca, PE and deep vein phlebitis during 5 years of treatment with Ca, PE and deep vein phlebitis during 5 years of treatment with conjugated equine estrogen and medroxyprogesterone conjugated equine estrogen and medroxyprogesterone (Prempro®). Subsequent analysis of these data showed no (Prempro®). Subsequent analysis of these data showed no increase in cardiovascular disease in women starting treatment increase in cardiovascular disease in women starting treatment within 10 years of menopause. In the estrogen only arm of WHI, within 10 years of menopause. In the estrogen only arm of WHI, no increase in breast cancer incidence was noted over 7.1 no increase in breast cancer incidence was noted over 7.1 years of treatment., Because of the risks, ET/HT should be used years of treatment., Because of the risks, ET/HT should be used in the lowest effective doses for the shortest duration to meet in the lowest effective doses for the shortest duration to meet treatment goals. When ET/HT use is considered solely for treatment goals. When ET/HT use is considered solely for prevention of osteoporosis, the FDA recommends that prevention of osteoporosis, the FDA recommends that approved non-estrogen treatments should first be carefully approved non-estrogen treatments should first be carefully considered.considered.

Estrogen Agonist/Antagonist (formerly known as Estrogen Agonist/Antagonist (formerly known as SERMs)SERMs)

– Raloxifene or Evista® is approved by the FDA for Raloxifene or Evista® is approved by the FDA for both prevention and treatment of osteoporosis in both prevention and treatment of osteoporosis in postmenopausal women. It reduces the risk of postmenopausal women. It reduces the risk of vertebral fractures by about 30% in patients with vertebral fractures by about 30% in patients with a prior vertebral fracture and by about 55% in a prior vertebral fracture and by about 55% in patients without a prior vertebral fracture over patients without a prior vertebral fracture over three years. It is indicated for the reduction in three years. It is indicated for the reduction in risk of invasive breast cancer in postmenopausal risk of invasive breast cancer in postmenopausal women with osteoporosis and does not reduce women with osteoporosis and does not reduce the risk of coronary heart disease. Raloxifene the risk of coronary heart disease. Raloxifene increases the risk of DVTto a degree similar to increases the risk of DVTto a degree similar to that observed with estrogen. It also increases that observed with estrogen. It also increases hot flashes. hot flashes.

Parathyroid HormoneParathyroid Hormone

– PTH(1-34), teriparatide, brand name: Forteo®. Teriparatide is PTH(1-34), teriparatide, brand name: Forteo®. Teriparatide is approved by the FDA for the treatment of osteoporosis in approved by the FDA for the treatment of osteoporosis in

– postmenopausal womenpostmenopausal women– men at high risk for fracture. men at high risk for fracture. – osteoporosis associated with sustained systemic glucocorticoid osteoporosis associated with sustained systemic glucocorticoid

therapy.therapy.– To increase bone mass in men with primary or hypogonadal To increase bone mass in men with primary or hypogonadal

osteoporosis. It is an anabolic (bone-building) agent osteoporosis. It is an anabolic (bone-building) agent administered by daily subcutaneous injection. Teriparatide in a administered by daily subcutaneous injection. Teriparatide in a dose of 20 μg daily was shown to decrease the risk of vertebral dose of 20 μg daily was shown to decrease the risk of vertebral fractures by 65 % and non-vertebral fractures by 53 %t in fractures by 65 % and non-vertebral fractures by 53 %t in patients with osteoporosis, after an average of 18 months of patients with osteoporosis, after an average of 18 months of therapy. therapy.

With Teriparatide some patients experience leg cramps With Teriparatide some patients experience leg cramps and dizziness. Because it caused an increase in the and dizziness. Because it caused an increase in the incidence of osteosarcoma in rats, patients with an incidence of osteosarcoma in rats, patients with an increased risk of osteosarcoma (e.g., patients with Paget’s increased risk of osteosarcoma (e.g., patients with Paget’s disease of bone) and those having prior radiation therapy disease of bone) and those having prior radiation therapy of the skeleton, bone metastases, hypercalcemia or a of the skeleton, bone metastases, hypercalcemia or a history of skeletal malignancy should not receive history of skeletal malignancy should not receive teriparatide therapy. It is common practice to follow teriparatide therapy. It is common practice to follow teriparatide treatment with an antiresorptive agent, usually teriparatide treatment with an antiresorptive agent, usually a bisphosphonate, to maintain or further increase BMD.a bisphosphonate, to maintain or further increase BMD.

TeriparatideTeriparatide

↑↑new bone formationnew bone formation Daily injectionDaily injection Given 12-24 monthsGiven 12-24 months Reserved for patients with Reserved for patients with

continued bone loss or continued bone loss or fracture on bisphosphonatesfracture on bisphosphonates

MONITORING EFFECTIVENESS OF TREATMENTMONITORING EFFECTIVENESS OF TREATMENT

NOF and Medicare guidelines NOF and Medicare guidelines recommenda DEXA scan every two recommenda DEXA scan every two years, but more frequent scans may be years, but more frequent scans may be warranted in certain clinical situations.warranted in certain clinical situations.

Central DXA. Central DXA. Central DXA assessment Central DXA assessment of the hip or spine is currently the “gold of the hip or spine is currently the “gold standard” for serial assessment of BMD. standard” for serial assessment of BMD.

CONCLUSION:CONCLUSION:

Osteoporosis or decreased bone density is a Osteoporosis or decreased bone density is a preventable condition with complications preventable condition with complications including fractures of the hip or spine which including fractures of the hip or spine which can compromise the quality of life in the later can compromise the quality of life in the later years. It can be reversed or prevented by years. It can be reversed or prevented by simple measures of changing you sedentary simple measures of changing you sedentary life style with weight bearing regular life style with weight bearing regular exercising and improving your diet to exercising and improving your diet to include calcium and vitamin D.include calcium and vitamin D.

THE ENDTHE END

THANK THANK YOUYOU

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