Comprehensive Review of Osteoporosis. Alyse Chandler, PharmD, BCPS, CDE March 11, 2018

Transcription

1 Comprehensive Review of Osteoporosis Alyse Chandler, PharmD, BCPS, CDE March 11, 2018

2 Objectives At the completion of this activity, the pharmacist will be able to: 1. Evaluate AACE/ACE 2016 osteoporosis guidelines 2. Recall osteoporosis medications and their role in management 3. Utilize clinical pearls in the management of osteoporosis 4. Discuss new evidence and studies related to osteoporosis

3 Objectives At the completion of this activity, the pharmacy technician will be able to: 1. Recall names of medications used commonly for management of osteoporosis 2. Identify routes of administration for osteoporosis medications 3. Discuss clinical pearls related to osteoporosis medications including side effects and therapeutic contraindications

4 Disclosure I have nothing to disclose

5 Public Health Impact 10.2 million Americans have osteoporosis 2 million osteoporosis-related factures occur annually 70% in women Age is an important risk factor By age 60, half of Caucasian women have osteoporosis or osteopenia

6 Fractures by skeletal site Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A., Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States J Bone Miner Res. 2007;22:

7 Definition & Diagnosis Sile t disorder of o e stre gth s i reased risk of fracture 2016 AACE Diagnosis of Osteoporosis in Postmenopausal Women 1. T-score -2.5 or below in the lumbar spine, femoral neck, total, and/or 33% (one-third radius) 2. Low-trauma spine or hip fracture (regardless of Bone Mineral Density [BMD]) 3. Osteopenia or low bone mass (T-score between -1 and - 2.5) with a fragility fracture of proximal humerus, pelvis, or possibly distal forearm 4. Low bone mass or osteopenia and high FRAX fracture probability based on country-specific thresholds

8 World Health Organization Criteria for Classification of Osteopenia and Osteoporosis Category T-Score Normal -1.0 or above Low bone mass (osteopenia) Between -1.0 and -2.5 Osteoporosis -2.5 or below

9 Diagnosis and Clinical Manifestations Fractures are the single most important manifestation of postmenopausal osteoporosis Caused by low-energy injuries (i.e., fall from standing height) Can be diagnosed with or without fragility fractures Vertebral fractures may occur during daily activities without fall

10 Risk factors Prior fracture without major trauma (except fingers, toes, skull) after age 50 Age 65 years or older Low body weight (<57.6 kg [127 lbs]) Family history of osteoporosis or fractures Secondary osteoporosis Height loss or kyphosis Risk factors for falling Excessive alcohol intake (3 or more drinks daily) Early menopause Smoking

11 Secondary Causes of Osteoporosis Endocrine or metabolic causes Nutritional/GI conditions Drugs Disorders of collagen metabolism Other Acromegaly Diabetes mellitus Type 1Type 2 Growth hormone deficiency Hypercortisolism Hyperparathyroidism Hyperthyroidism Hypogonadism Hypophosphatasia Porphyria Pregnancy Alcoholism Anorexia nervosa Calcium deficiency Chronic liver disease Malabsorption syndromes/ malnutrition (including celiac disease, cystic fi rosis, Croh s disease, and gastric resection or bypass) Total parenteral nutrition Vitamin D deficiency Antiepileptic drugs Aromatase inhibitors Chemotherapy/ immunosuppressant s Depo-Provera Glucocorticoids Gonadotropinreleasing hormone agents Heparin Lithium Proton pump inhibitors Selective serotonin reuptake inhibitors Thiazolidinediones Thyroid hormone (in supraphysiologic doses) Ehlers-Danlos syndrome Homocystinuria due to cystathionine deficiency Marfan syndrome Osteogenesis imperfect AIDS/HIV Ankylosing spondylitis Chronic obstructive pulmonary disease Gaucher disease Hemophilia Hypercalciuria Immobilization Major depression Myeloma and some cancers Organ transplantation Renal insufficiency/ failure Renal tubular acidosis Rheumatoid arthritis Systemic mastocytosis Thalassemia

12 FRAX tool

13 Bone Density Scores T-score: number of SDs from the normal young-adult mean values Used for diagnostic classification for postmenopausal women Z-score: number of SDs from the normal mean value for age-, race- or ethnicity-, and sexmatched control subjects Used for diagnostic classification for premenopausal women

14 Lab evaluation CBC CMP Vitamin D 25-(OH) PTH Phosphate Thyroid function test 24-hour urine collection (calcium, sodium, and creatinine)* *After the vitamin D is replaced and has been taking calcium (1,000-1,200 mg/day) x 2 weeks Celiac antibodies if suspicion of malabsorption

15 Prevention of Fractures and Bone Loss Adequate intake of calcium and vitamin D LIFELONG participation of regular, weightbearing, resistance exercise, and balanceimproving exercise Avoid tobacco and excessive alcohol Eliminate potential risk factors for falling

16 Vitamin D Major role in calcium absorption May enhance the response to bisphosphonate therapy, increase bone mineral density, and prevent fractures Shown to improve muscle strength, balance, and fall risk

17 Vitamin D AACE and Endocrine Society recommend Vitamin D 25-(OH) levels of 30ng/ml or higher For vitamin D deficient patients, may treat with 50,000 IU vitamin D2 or vitamin D3 daily x 8-12 weeks Maintenance therapy of vitamin D3 1,000 IU to 2,000 IU daily Food sources are limited. Recommend vitamin D supplementation

18 Calcium Fundamental aspect of osteoporosis prevention at any age Average daily calcium intake among American adults is about half of what is recommended Recommended calcium intake (diet and supplements) is 1,200 mg/day Optimal intake of supplements is controversial

19 Calcium Studies: Lo g ter al iu i take a d rates of all ause a d cardiovascular mortality: community based prospe ti e lo gitudi al ohort stud : More than 1,500 mg/day was associated with a hazard ratio of 1.40 (95% CI, ) for all cause mortality Relatio of al iu, ita i D, a d dair food i take to ischemic heart disease mortality among post e opausal o e : Low calcium intake (<700 mg/day compared with 1,400 mg/day) was associated with increased cardiovascular risks

20 Calcium Supplementation Calcium carbonate Least expensive Smallest number of tablets May cause more GI complaints (i.e., bloating and/or constipation) Calcium citrate More expensive Requires more tablets Does NOT require gastric acid for absorption; can be taken with or without food Causes less GI complaints

21 Calcium Supplementation Dosage forms: tablets, soft chews, and gummies *Optimal absorption: should not exceed mg per dose* Counseling points for patients: they will need to divide their dose

22 Other clinical pearls Magnesium Counter constipation associated with calcium Caffeine: limit caffeine intake to less than 1 to 2 servings (8-12 ounces/serving) of caffeinated drinks per day Leads to a slight decrease in intestinal calcium absorption and increase in urinary calcium excretion

23 Other clinical pearls Adequate protein minimizes bone loss Postmenopausal women should limit alcohol to no more than 3 drinks daily Smoking should be avoided Regular weight-bearing, resistance, and back/posture exercises should be encouraged throughout life Prevention of falls Hip protectors do not reduce falls but help decrease risk of fracture

24 Who Needs Treatment? AACE recommend the following: Patients with osteopenia/low bone mass + fragility fracture of the hip or spine T-score of -2.5 or lower in the spine, femoral neck, total hip, or 33% radius T-score between -1.0 and -2.5 in the spine, femoral neck, total hip, or 33%, if the FRAX 10- year probability for major osteoporotic fracture is 20% or higher or the 10-year probability of hip fracture is 3% or greater (US) or above the country-specific threshold in other countries or regions

25 Bisphosphonates Bind to hydroxyapatite in bone and reduce the activity of bone-resorbing osteoclast Alendronate, ibandronate, risendronate, and zoledronic acid 3 of the 4 have evidence for broad-spectrum antifracture (ibandronate does not have this indication)

26 Drugs approved by FDA for Prevention and Treatment Drug Prevention Treatment Alendronate Ibandronate Risendronate 5mg PO daily 35mg PO weekly 2.5mg PO daily 150mg PO monthly 5mg PO daily 35mg PO weekly 150mg PO monthly 10mg PO daily 70mg PO weekly 70mg + Vitamin D PO weekly 2.5mg PO daily 150mg PO monthly 3mg IV every 3 mo 5mg PO daily 35mg PO weekly 150mg PO monthly Zoledronic Acid 5mg IV every 2 years 5mg IV every year

27 Oral Bisphosphonates Alendronate, Ibandronate, and Risendronate Take on an empty stomach in the morning with a full glass of water Wait 30 minutes before taking any other medications, eating, or drinking beverages (except water) Atelvia can be taken with or without food due to delayed-release formulation Do not lie down for at least 1 hour after taking medication

28 Contraindications to Hypersensitivity Hypocalcemia Bisphosphonates Reduced kidney function Risendronate and ibandronate: GFR <30 ml/min Alendronate and Zoledronic Acid: GRR <35 ml/min

29 Clinical pearl for bisphosphonates 30% of patients receiving IV bisphosphonates may have acute-phase reactions on first dose Counseling points for patients: May experience fever and myalgias (i.e, flu-like symptoms) for several days Acetaminophen can be taken 1 to 2 hours before treatment and reduce likelihood of reactions and can be used for after treatment for symptoms Patients should be taking calcium/vitamin D supplements with therapy Risk for Osteonecrosis of the Jaw (ONJ) and Atypical Femoral Fractures (AFF)

30 Denosumab Fully human monoclonal antibody Prevents receptor activator of nuclear factor kappa-b ligand (RANKL) from binding to its receptor, RANK. Result: reducing the differentiation of precursor cells into mature osteoclasts and function of activated osteoclasts

31 Drugs approved by FDA for Prevention and Treatment Drug Prevention Treatment Denosumab -- 60mg SQ every 6 mo

32 Clinical pearls for Denosumab Before starting therapy, correct calcium- and vitamin D deficiency, as well as hyperparathyroidism Patients should be taking a calcium/vitamin D supplements with therapy Risk for ONJ Drug holida is NOT re o e ded si e BMD decreases to baseline after stopping therapy for 2 years

33 Raloxifene Selective Estrogen Receptor Modulator (SERM) FDA approved for prevention/treatment of osteoporosis AND reduction of breast cancer in women with osteoporosis Only indicated to reduce risk for spine fracture Contraindications: History of VTE disease Women of childbearing potential Hypersensitivity

34 Drugs approved by FDA for Prevention and Treatment Drug Prevention Treatment Raloxifene 60mg PO daily 60mg PO daily

35 Clinical pearls for Raloxifene Option for patients with low BMD in the spine (but not in the hip) + high risk of breast cancer If hip fracture is high, can add bisphosphonate or denosumab to raloxifene therapy Raloxifene is associated with 3-fold increase in VTE Causes menopausal symptoms (i.e., hot flashes and night sweats) and leg cramps Skeletal benefits are lost quickly after 1-2 years of discontinuation of therapy

36 Calcitonin Injectable and nasal spray recombinant salmon calcitonin Only indicated in treatment of osteoporosis, not prevention Reduces the risk of new vertebral fractures Contraindication: Hypersensitivity: skin test is recommended

37 Drugs approved by FDA for Prevention and Treatment Drug Prevention Treatment Calcitonin IU intranasally once daily or 100 IU SQ every other day

38 Clinical pearls for Calcitonin Benefits are lost after 1-2 years after discontinuation of calcitonin Analgesic benefit: can be used in patients with acute painful vertebral fractures Side effects: SQ: nausea, local reactions, sweating, flushing Intranasally: rhinitis, epistaxis, irritation

39 Teriparatide Recombinant human PTH(1-34) anabolic agent Work by reducing bone resorption FDA indicated for patients with high risk for fracture or failed/intolerant to other osteoporosis therapy Approved for treatment of glucocorticoidinduced osteoporosis

40 Drugs approved by FDA for Prevention and Treatment Drug Prevention Treatment Teriparatide mcg SQ daily

41 Clinical pearls for Teriparatide Reduces risk of vertebral and nonvertebral fractures (does not reduce fractures in hips) Side effects: hypercalcemia, nausea, orthostatic hypotension, leg cramps *BOXED WARNING*: occurrence of osteosarcomas in 1 strain of rats treated with high doses (3-50x higher than human equivalent dose) Annual incidence of osteosarcoma in women 50 years or older in general population is 1 in 250,000. Occurrence in teriparatide patients is unknown

42 Clinical pearls for Teriparatide Do not give to patients with primary or secondary untreated/unresolved hyperparathyroidism Not approved for treatment after 2 years After treatment has been discontinued, bone density declines quickly over 1-2 years

43 Evidence for Fracture Risk Reduction Drug Vertebral Nonvertebral Hip Alendronate Yes Yes Yes Ibandronate Yes No* No* Risendronate Yes Yes Yes Zoledronic Acid Yes Yes Yes Denosumab Yes Yes Yes Raloxifene Yes No* No* Calcitonin Yes No* No* Teriparatide Yes Yes No* *No effect demonstrated ACCE/ACE Postmenopausal Osteoporosis CPG, Endocr Pract (Suppl 4)

44 Monitoring Treatment Check BMD every 1-2 years (at the same facility) Assess for noncompliance, medications, or secondary causes of osteoporosis in patients with declining BMD Treatment failure defined as recurrent fractures in a patient who is compliant or significant decrease in BMD Goal: fracture prevention. No treatment can eliminate the risk

45 Monitoring Treatment AACE guidelines agree long-term bisphosphonate patients who are at high risk and remain at high risk receive oral treatment for 10 years Use teriparatide or ralo ife e duri g drug holida for high risk patients Lo er risk patie ts a e o sidered for drug holida after 5 years on oral bisphosphonates and 3 years on IV zoledronic acid No therap is eeded duri g drug holida for low risk patients

46 New Therapies in Management Abaloparatide (similar to teriparatide): Approved in April mcg once daily Treatment of osteoporosis at high risk for fracture Limited to only 2 years of therapy Same BOXED WARNING for osteosarcomas

47 Potential new therapy in osteoporosis Romosozumab or Alendronate for Fracture Pre e tio i Wo e ith Osteoporosis 4,093 women with average age of 74; history of osteoporosis and fractures Treated with either alendronate or romosozumab (antibody that blocks sclerostin) After 12 months, all patients received alendronate x 12 months Results: vertebral fracture was 48% lower in romosozumab compared with alendronate

48 Case RS is a 63 year old Caucasian female with PMH significant for T1DM, GERD, HTN, and HLD who presents to your clinic for her annual physical Social history: Smoking: denies but quit smoking 20 years ago (history of smoking 10 pack years) Alcohol: drinks socially several times per week and may have up to 4 drinks in one evening Exercise: she is sedentary but gardens on occasion Vitals: Weight: 95 lbs (43 kg) Height: 62 inches (157 cm) Blood pressure: 132/82 mmhg Pulse: 95 bpm

49 Case Family history is positive for osteoporosis (2 sisters with diagnosis) Medication list: ASA 81mg daily Levemir 12 units HS Novolog TID with meals sliding scale Pravastatin 40mg HS Losartan 25mg daily Omeprazole 20mg BID

50 Case Which of the following are risk factors for developing osteoporosis in RS? a. Smoking history b. Type 1 diabetes c. PPI therapy d. Low weight e. All of the above

51 Case RS labs came back and all were WNL. Current GFR is 65 ml/min DEXA scan indicated her T-Score is -2.3 What is her diagnosis? a. Osteopenia b. Osteoporosis c. None of the above

52 Case Which of the following therapies would be appropriate for RS? a. Zoledronic Acid 5mg IV once a year b. Denosumab 60mg every 6 months c. Alendronate 35mg weekly d. Teriparatide 20mcg daily

53 Case RS comes back one year later for her annual physical. She is doing well with the therapy started at her last physical and notes no real changes but did not start calcium/vitamin D with therapy as previously instructed since she has difficulty swallowing large pills. Vitals: Weight: 100 lbs (45 kg) Height: 61 inches (154 cm) Blood pressure: 133/88 mmhg Pulse: 91 bpm

54 Case RS labs came back and continue to be WNL, except her Vitamin D (currently 20ng/ml). Current GFR is 63 ml/min DEXA scan indicated her T-score is -2.6 What is her diagnosis? a. Osteopenia b. Osteoporosis c. None of the above

55 Case Take away counseling points from RS: Needs to be on a calcium + vitamin D supplement (switch to chewables or gummies) Decrease amount of alcohol per day (no more than 2 drinks per day) Start regular weight-bearing and resistance exercises Will eed to start treat e t doses of osteoporosis therapy (preferably none PO therapy)

56 QUESTIONS?