Osteoporosis Screening and Treatment Guidelines

PAGE 1. Algorithm

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2. Clinical Highlights and Recommendations

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3. Recommendations for Baseline Bone Mineral Density Screening (Central DEXA)

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4. Recommendations for Repeat Bone Mineral Density Scanning (Central DEXA)

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5. Recommendations for the Initiation of Therapy

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6. Table1: Common Sources of Calcium and Vitamin D

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7. Table 2: Medical Conditions Associated with an Increased Risk of Osteoporosis in Adults

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8. Table 3: Medications Associated with an Increased Risk of Osteoporosis in Adults

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9. Table 4: Recommended Pharmacological Agents for Osteoporosis

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10. Summary of ACOG Recommendations

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11. Summary of USPSTF Recommendations

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12. References

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Written By:Honeylit Cueco, PharmD; Neil Murphy, MD; Molly Southworth, MD; Date: 5/20/2013 MCH CCBG Approval Date: 3/2/11

This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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*For men: see page 4, Recommendations for Initiation of Therapy Osteoporosis Screening and Treatment Guideline

A summary of clinical recommendations for screening, repeat scanning and treatment options is provided on pages 3-7 of this guideline.

Clinical Highlights and Recommendations

1. Advise all patients of both genders to consume adequate amounts of calcium and vitamin D (Table 1). Dietary intake is preferable but supplements are often needed to accomplish goals: a. Calcium: 1000 -1500 mg/day. b. Vitamin D: 800 – 1000 IU/day for people over 50 years of age. 400 to 800 IU/day for healthy people age 19 to 49 years of age. 2. Counsel women of appropriate ages regarding the risk of osteoporosis associated with menopause, the importance of achieving and maintaining optimal bone density in younger years, and the importance of avoiding additional risk factors throughout life. 3. Recommend regular weight-bearing and muscle-strengthening exercise for all patients, to preserve bone density and to reduce the risk of falls and fractures, in addition to other health benefits. 4. Advise all patients to avoid tobacco and excessive alcohol intake. 5. Recommend baseline central DEXA scanning (AP spine and hip) to patients who meet the ANMC indications for baseline DEXA scan, detailed below. 6. All patients diagnosed with osteoporosis should be evaluated for secondary causes, such as other disease processes or medications which cause osteoporosis (see Table 2). Secondary causes should be modified/treated whenever possible.

Recommendations for Baseline Bone Mineral Density Screening (Central DEXA ) 1. Bone mineral density testing (BMD) by central DEXA should be recommended for all postmenopausal women aged 65 years or older. 2. Central DEXA should be recommended for post-menopausal women of any age with additional risk factors for osteoporosis or fracture. Pertinent additional risk factors include: a. Family history of osteoporosis with fractures (mother or sister) b. Weight -1.0, no new risk factors: repeat in 5 - 10 years. Baseline T scores < -1.0, not on therapy, with ongoing risk factors: repeat in 2-4 years. Baseline T scores < -1.5, monitoring therapy: repeat in 2 years. Aggressive disease progression suspected, based on clinical situation: may repeat in 6-12 months, but this should be fairly uncommon.

Recommendations for Initiation of Therapy (Table 4) Postmenopausal women and men age 50 and older presenting with the following should be considered for treatment: 1. A hip or vertebral (clinical or morphometric) fracture 2. T-score < -2.5 at the femoral neck, lumbar spine or hip after appropriate evaluation to exclude secondary causes 3. Low bone mass (T-score between -1.0 and -2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture > 3% or a 10-year probability of a major osteoporosis-related fracture >20% based on the US-adapted WHO absolute fracture risk model (FRAX®; www.NOF.org and www.shef.ac.uk/FRAX) 4. ALL patients should also receive adequate calcium and vitamin D, participate in weight bearing exercise, and avoid additional risk factors. 5. No pharmacologic treatment should be considered indefinite. Treatment duration decisions need to be individualized. (1)

Table 1: Common Sources of Calcium and Vitamin D

Dietary Sources of Calcium Milk 300 mg Ca per 8 oz serving Yogurt 400 mg Ca per 8 oz serving Cheese 200 mg Ca per 1 oz serving Fortified foods or juices 80-1000 mg Ca per serving, as per label Alaska Native chum, raw 7mg Ca/100grams (3.5ounces) Alaska Native red, smoked, canned 69mg Ca/100grams (3.5ounces) Common Supplements available at ANMC Calcium carbonate,1250 mg (on formulary) 500 mg elemental calcium per tab Oscal (combination Ca and vit D, on 500 mg elemental calcium per tab formulary) 200 IU vitamin D per tab Vitamin D3 (cholecalciferal) 400 IU or 1000 IU Typical Regimens Vitamin D is typically obtained from a combination of dairy products, other calcium-rich foods, sunlight, and/or OTC multiple vitamins or Ca/Vitamin D combination pills. Other dietary sources of vitamin D include vitamin D-fortified milk, cereals, egg yolks, fatty fish, and liver. Example: One tablet BID of Oscal (on formulary) would contain 1000 mg calcium plus 400 IU vitamin D, appropriate for many patients who consume very little dairy or other calcium-rich food. One tablet per This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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day would be appropriate for a person consuming two calcium-rich foods/day.

Table 2: Medical Conditions Associated with an Increased Risk of Osteoporosis in Adults Hyperparathyroidism

Post-transplant disease

Hyperprolactinemia

Premature ovarian failure

Hypogonadism, primary or secondary

Prior fracture as an adult

Alcoholism Amyloidosis

Hypophosphatasia

Androgen insufficiency

Idiopathic hypercalciuria

Ankylosing spondylitis

Idiopathic scoliosis

Anorexia nervosa and bulimia

Inadequate diet

Athletic amenorrhea

Inflammatory bowel disease

Celiac disease

Insulin-dependent diabetes mellitus

Spinal cord transsection

Acquired Immunodeficiency Syndrome Adrenal insufficiency

Rheumatoid arthritis Riley-Day syndrome Sarcoidosis Severe liver disease, especially primary biliary cirrhosis Sickle cell disease Chronic metabolic acidosis Lupus

Sprue

Chronic obstructive pulmonary disease

Lymphoma and leukemia

Stroke

Congenital porphyria

Malabsorptive syndromes

Systemic mastocytosis

Congestive heart failure

Marphan syndrome

Thalassemia

Cushing’s syndrome

Mastocytosis

Thyrotoxicosis

Cystic fibrosis

Menkes steely hair syndrome

Tumor secretion of parathyroid hormone related peptide

Depression

Multiple myeloma

Diabetes mellitus

Multiple sclerosis

Turner’s & Klinefelter’s syndromes

Eating disorders

Muscular dystrophy

Weight loss

Ehlers-Danlos

Osteogenesis imperfecta

Emphysema

Panhypopituitarism

This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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End stage renal disease

Pancreatic disease

Epilepsy

Parental history of hip fracture

Female athlete triad

Pernicious anemia

Gastrectomy/Gastric bypass/G.I. surgery

Porphyria

Gaucher’s disease Glycogen storage diseases Hemochromatosis Hemophilia Homocystinuria Hypophosphatasia

Table 3: Medications Associated with an Increased Risk of Osteoporosis in Adults

Aluminum

Heparin (long-term)

Provera depo (chronic)

Anticonvulsants

Lithium

Thyroid hormone (supraphysiologic)

Aromatase inhibitors

Methotrexate

Barbiturates

Proton Pump Inhibitors

Cancer chemotherapeutic drugs

Selective Serotonin Reuptake Inhibitors

Tamoxifen (premenopausal) Total Parenteral Nutrition

Cyclosporine A and tacrolimus Pioglitazone (Actos) Glucocorticosteroids > 5mg/day of prednisone or equivalent for 3 months or longer

Rosiglitazone (Avandia)

Gonadotropin hormone releasing hormone agonists

Table 4: Recommended Pharmacological Agents for Osteoporosis (latest 5/20/13) Medication

Indications

Dose Administration

Reduction in fracture

Adverse drug reactions

Contraindications

This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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risk Calcitonin Calcitoninsalmon nasal spray

TREATMENT Postmenopausal osteoporosis in women with at least 5 years postmenopause with low bone mass relative to healthy premenopausal females Estrogens (see Bone Health Discussion text) Estrogens PREVENTION Postmenopausal osteoporosis

Bisphosphonates Alendronate PREVENTION (Fosamax) • Postmenopausal osteoporosis TREATMENT • Postmenopausal osteoporosis • Osteoporosis in men • Glucocorticoidinduced osteoporosis in men and women

Nasal spray: 200 units intranasal daily, alternate nostrils daily

Vert: + Nonvert: Hip: -

Nausea Epistaxis Flushing Rhinitis

Hypersensitivity

Varies by manufacturer

Vert: +++ Nonvert: ++ Hip: +++

BLACK BOXED WARNING: Estrogens increase the risk of endometrial cancer; monitor for abnormal vaginal bleeding. Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. Increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and DVT in postmenopausal women (50 to 79 years of age) have been reported. An increased risk of developing probable dementia in postmenopausal women 65 years of age or older has also been reported • Bloating • Headache • Breast tenderness • Uterine bleeding • Those with an intact uterus must also take a progestin • Breast cancer • Increased risk of myocardial infarction, stroke, venous thrombosis or pulmonary embolism • Comments: Dementia, gall bladder disease, hypercalcemia, visual abnormalities, hypertension are also mentioned

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PREVENTION 35 mg tab po weekly

Vert: +++ Nonvert: ++ Hip: +++

TREATMENT Postmenopausal: 70 mg tab po weekly Glucocorticoid induced:

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Pregnancy History of thromboembolic disorders Breast cancer (except appropriately selected patients treated for metastatic disease) Estrogen dependent neoplasia Undiagnosed abnormal vaginal bleeding Hypersensitivity Liver dysfunction or disease, active or recent (within 1 year) Stroke or MI CVD

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Esophagitis, abdominal pain, diarrhea Jaw osteonecrosis (rare), musculoskeletal pain, dyspepsia, acid regurgitation, esophageal ulcer, dysphagia, flu-like symptoms (rare postmarket experience)

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• • •

This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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Abnormalities of the esophagus that delay esophageal emptying Hypersensitivity Uncorrected hypocalcemia Not recommended for patients with CrCl < 35 ml/min

35 mg po weekly; 70mg po weekly in postmenopausal women not receiving estrogen Selective Estrogen Receptor Modulator (SERM) Raloxifene TREATMENT & 60 mg po daily PREVENTION (Evista) Postmenopausal osteoporosis 1. Unsuccessful bisphosphonate therapy 2. Contraindication to bisphosphates 3. History of breast cancer 4. No thromboembolic events

Teriparatide (Forteo) (PTH)

Osteoporosis primary or hypogonadal, glucocorticoid-induced osteoporosis, postmenopausal osteoporosis

20mcg SubQ daily for not more than 2 years

Vert: +++ women without fracture ++ women with fracture Nonvert: Hip: -

BLACK BOXED WARNING: Raloxifene has been associated with increased risk of thromboembolism (DVT, PE) and superficialthrombophlebitis (greatest risk during first 4 months of treatment); risk is similar to reported risk of HRT. Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. Consider risk-benefit balance in women at risk for stroke • Hot flashes • Leg cramps • Increased risk of venous thromboembolic events

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Vert: +++ Non-vert: +++ Hip: N/A

BLACK BOXED WARNING: Show to cause an increase in the incidence of osteosarcoma in male and female rats, dependent on dose and duration of treatment. • Orthostatic hypotension • Nausea • Increase in serum calcium • May increase risk of digoxin toxicity • Increase in urinary calcium

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Hypersensitivity to, or any component of the formulation

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Avoid in patients with increased risk of osteosarcoma (including Paget’s disease, prior radiation, unexplained elevation of alkaline phosphatase, or in patients with open epiphyses)

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Do not use in patients with a history of skeletal metastases, hyperparathyroidism or pre-existing hypercalcemia

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Not for use in patients with metabolic bone disease other than osteoporosis. Should not be administered to pregnant or breastfeeding women

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Zoledronic Acid (Reclast) (Bisphosphonate)

Pregnancy History of venous thromboembolism Hypersensitivity Nursing women

PREVENTION See below. (*) Vert: +++ FDA warning 2011: CI • Hypersensitivity to Non-vert: in patients with renal • Osteoporosis in zoledronic acid or ++ impairment postmenopausal any of its excipients This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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women Glucocorticoidinduced osteoporosis

Hip: ++ •

TREATMENT • Osteoporosis in men and postmenopausal women • Glucocorticoidinduced osteoporosis • Osteoporosis, secondary prophylaxis in patients with recent low-trauma hip fracture (Shown to decrease mortality in high risk patients suffering from hip fx (only bisphosphonate to do this) 1.

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CrCl 50% reduction; ++ 40-50% reduction; + < 40% reduction; - unable to show reduced risk; N/A No data available from RCT

(*) Zoledronic Acid Dosing: • Osteoporosis in men, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis: A single 5mg infusion once a year given intravenously (IV) over no less than 15 minutes. Note for concomitant therapy: Patients must be adequately supplemented with calcium and vitamin D if dietary intake is not sufficient. An average of at least 1,200 mg of calcium and 800 to 1,000 units of vitamin D daily is recommended. •

Prevention of osteoporosis in postmenopausal women: 5mg infusion given IV once every 2 years over no less than 15 minutes. Note for concomitant therapy: Patients must be adequately supplemented with calcium and vitamin D if dietary intake is not sufficient. An average of at least 1,200 mg of calcium and 800 to 1,000 units of vitamin D daily is recommended.

Summary of ACOG recommendations for women Level A The following are based on good and consistent scientific evidence •

Treatment should be recommended for: — Women with a T-score of –2.5 or less — Women who have had low-trauma fracture — Women who have a T-score from –1 to –2.5 and a FRAX score greater than or equal to 3% for risk of hip fracture or a FRAX score greater than or equal to 20% for risk of a major osteoporotic fracture (defined as forearm, hip, shoulder, or clinical spine fracture) or both in the next 10 years

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FDA-approved therapies should be used for medical treatment: raloxifene, bisphosphonates, PTH, denosumab, calcitonin.

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Bone density screening for women should begin at age 65 years. Dual-energy X-ray absorptiometry screening can be used selectively for women younger than 65 years if they are postmenopausal and have other significant risk factors for osteoporosis or fracture.

Level B The following are based on limited or inconsistent scientific evidence This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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In the absence of new risk factors, DXA screening should not be performed more frequently than every 2 years.

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In the absence of new risk factors, DXA monitoring of therapy should not be repeated once BMD has been determined to be stable or improved.

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Women should be counseled about lifestyle factors that may affect BMD and fracture risk: smoking, poor nutrition and excessive weight loss, weight-bearing and muscle-strengthening exercise, and fallprevention measures.

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Women should be advised of current IOM calcium and vitamin D recommendations.

Level C The following recommendations are based primarily on consensus and expert opinion Women should be counseled on the risks of osteoporosis and related fragility fractures. Such counseling should be part of the annual gynecologic examination Osteoporosis. Practice Bulletin No. 129. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:718–34.

AHRQ: USPSTF Summary of Recommendations •

The U.S. Preventive Services Task Force (USPSTF) recommends that the following women should be screened routinely for osteoporosis: women aged 65 and older as well as younger women whose fracture risk is equal to or greater than that of a 65-year-old Caucasian woman with no additional risk factors (using FRAX algorithm). Rating: B Recommendation. Rationale: The USPSTF found good evidence that the risk for osteoporosis and fracture increases with age and other factors, that bone density measurements accurately predict the risk for fractures in the short-term, and that treating asymptomatic women with osteoporosis reduces their risk for fracture. The USPSTF concludes that the benefits of screening and treatment are of at least moderate magnitude for women at increased risk by virtue of age or presence of other risk factors.

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The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men. Rating: I statement.

Rationale: Research is needed to test the effectiveness of drug therapies for osteoporosis in men who do not have a history of fractures. The results of ongoing randomized trials of bisphosphonates for fracture prevention in men at high risk for fractures could help to assess whether these drugs are effective in men. Assuming that the relative benefits and harms of therapy in men are similar to those in women, the men most likely to benefit from screening would have 10-year risks for osteoporotic fracture equal to or greater than those of 65-year-old white women who have no additional risk factors.

This guideline is designed for general use for most patients but may need to be adapted to meet the special needs of a specific customer-owner as determined by the customer-owner’s provider

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Table 5. Osteoporosis Screening Recommendations of Other Organizations Recommendations Organization

Women

Men

National Osteoporosis Foundation

BMD testing for all women ≥65 y and postmenopausal women