Chau Nguyen, D.O. Rheumatologist Clinical Assistant Professor of Internal Medicine at Western University of Health Sciences

Transcription

1 Chau Nguyen, D.O Rheumatologist Clinical Assistant Professor of Internal Medicine at Western University of Health Sciences

2 I do not have any relationship with the manufacturer of any commercial products and/or provider of commercial services.

3 Management of osteoporosis Indications for treatment Pharmacological treatment

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5 Low bone mass and micro-architectural deterioration of bone tissue = susceptibility to fracture. *Consensus Development Conference: Diagnosis, Prophylaxis, and Treatment of Osteoporosis. Am J Med. 1991;90:107. Photos courtesy of David Dempster

6 Alcohol Abuse Smoking Glucocorticoids Vitamin D Insufficiency Inadequate physical activity Low Calcium Intake Fractures Low body mass index NOF 2013 guide

7 All women >65 y/o All men >70 y/o All women and men y/o with risk factors Perimenopausal women with risk factors National Osteoporosis Foundation Clinicians Guide, June, 2014.

8 1-2 years initiation treatment and every 2 years afterward. Glucocorticoids: 6 months after initiation steroids treatment. National Osteoporosis Foundation Clinicians Guide, June, 2014.

9 T-score = Patients BMD- Young Normal Mean BMD SD of Young Normal Only applicable for postmenopausal women or men over 50 Z-scores = Patients BMD- Age Matched Mean BMD SD of Age Matched Appropriate for children and healthy adults < 50

10 T- score Normal Low Bone Mass (Osteopenia) Osteoporosis Severe Osteoporosis Equal to -1.0 or higher Between -1.0 and -2.5 Equal to -2.5 or lower Equal to -2.5 or lower with fracture

11 Based on risk factors, femoral neck BMD. Assess: 10-year risk of hip fracture >3% 10-year risk of all osteoporotic fractures- >20%

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13 NOF criteria for using FRAX to assist with treatment decision: 1. Untreated postmenopausal woman or a man >50 years old 2. With low bone mass (T-score -1.0 and -2.5) 3. With no prior hip or vertebral FX (clinical or morphometric) 4. And an evaluable hip for DXA study

14 Non-traumatic fractures and osteopenia Osteoporosis with T-score < -2.5 Osteopenia with positive Frax score

15 Nutritional Vitamin D deficiency, ETOH, smoking, Ca deficiency Diseases COPD, RA, Crohn s, Celiac, Gastric bypass Endocrine Hypogonadism, DM, hyperthyroidism Medications GCs( 5mg daily for 3 months), Anticonvulsants, Aromatase inhibitors, GnRH agonists, opioids, Immunosuppressants (cyclosporine, cyclophosphamide), possible meds: anti depressants, SSRIs, PPIs, TZDs

16 Most common form of secondary osteoporosis Bone loss can be rapid (up to 20% in 6 months) Fractures common (up to 50% of patients on chronic steroids) Fractures occur at higher BMD than typical osteoporosis patients Often untreated (only 10% have a DXA, 40% on osteoporosis medication) The International Society for Clinical Densitometry (ISCD). Feb,2014 Orlando

17 Daily Dose Treatment >7.5 mg Yes <7.5 mg FRAX 3% hip or 20% of major fracture FRAX >3% hip or >20% of major fracture No Yes

18 Z-score > -3 No fracture and on prednisone >30mg/d for >1 month. Low-trauma fracture And < 7.5 mg/d (1-3 months) Z-score < -3 Fracture on any dose of chronic prednisone. No fracture and on 7.5 mg/d > 3 months

19 Basic: CBC, chemistry panel, TSH, 25(OH)D, 24 hour urine calcium/creatinine. Additional: bone turnover markers N-telopeptide of type 1 collagen (NTX) C-terminal telopeptide of type 1 collagen (CTX)

20 Education on the risk factors. Diet of total calcium 1,000 mg/ day Vitamin D intake 1,000 IU/ day Regular weight-bearing Modifications of the risk factors for falls

21 Antiresorptive: 1. Bisphosphonates (Alendronate, Ibandronate, Risedronate and Zoledronic acid) 2. Calcitonin (not used anymore) 3. Conjugated Estrogen 4. Raloxifene 5. RANK ligand inhibitor :Denosumab Anabolic therapy - Parathyroid hormone: Teriparatide, Abaloparatide

22 Prevent bone loss Prevent micro-architectural deterioration Promote mineralization

23 Name Alendronate Fosamax Risedronate Actonel Ibandronate Boniva Zoledronic acid Reclast Route po daily or weekly po daily, weekly or monthly po monthly or IV q 3 months yearly IV

24 Hip fractures reduced 40% with: 1. Alendronate 2. Risedronate 3. Zoledronic acid Spine fractures reduced 50% in all ISCD. Feb,2014 Orlando clinical trials FIT, VERT, HIP, HORIZON

25 Poorly absorbed Not metabolized: 50% excreted by kidney, and 50% binds to bone High affinity to bone Binds preferentially at resorptive surfaces Induces osteoclast dysfunction Long skeletal half-life, can recycle

26 GI intolerance with oral agents Not recommended for GFR < ml/min Acute phase reaction with IV Hypocalcemia Chronic muscle/joint pain Oversuppression of bone turnover Osteonecrosis of the jaw (ONJ) Atypical femoral fractures

27 Risk factors for developing ONJ: Cancer, and anti-cancer therapy Dental implants, dental extractions, poorly fitting dentures, GCs, smoking and preexisting dental disease If the patient on po bisphosphonates > 3 years and needs dental surgery Stop 3 months before the procedure and restart after complete bone healing American Association of Oral and Maxillofacial Surgeons

28 Fractures of femoral diaphysis or in subtrochanteric region Transverse rather than spiral May begin with stress reaction or stress fracture of lateral femoral cortex which may be bilateral Prodromal pain in thigh or groin is common Often on other drugs, especially steroids or estrogen ISCD

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30 Antiresorptive, fully human monoclonal antibody, binds and inhibits RANKL (RANKL triggers activation of osteoclasts) BMD: increases at spine and hip Fracture: decreases spine, hip and nonvertebral fracture by 68%, 40%, 20% Injection SQ every 6 months Safety: increased infection risk

31 Teriparatide (Forteo) Abaloparatide (Tymlos)

32 Anabolic, hormone Increases BMD at spine and hip Increased Bone turnover markers Decreases spine 65%,and nonvertebral fractures 53% Limitations: Osteosarcoma in rats, limit of 2 years of therapy Daily subcutaneous injection High cost Neer RM, et al. N Engl J Med. 2001;344:1434

33 BMD: preserves/increases BMD Fractures: reduces spine, hip, and forearm fractures by 35%, 33% and 29% Extraskeletal considerations Relieves symptoms of estrogen deficiency Increases risk of breast cancer, VTE, coronary disease, stroke Endometrial cancer risk in unprotected uterus Reduces risk of colon cancer Cauley JA, et al. JAMA 2003;290:1729

34 Weak efficacy compared to bisphosphonates. No significant reduction in non-vertebral fractures or hip fractures. Increase rate of cancer. Bell et al. Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metb. 2000;85(5):1783.

35 SERM (selective estrogen receptor modulator) BMD: increases at spine and hip Fractures: reduces risk of vertebral fractures 30-50%, no proven benefit for hip or non-vertebral fractures Reduces risk of breast cancer (approved for prevention of breast cancer) Increases VTE risk, leg cramps Ettinger B, et al.jama.1999;282:637

36 Medication Spine Hip Estrogen Alendronate Risedronate Ibandronate Zoledronic acid Calcitonin ~ ~ Raloxifene Denosumab Teriparatide

37 Medication Spine Hip Nonvertebral Estrogen Alendronate Risedronate Ibandronate Zoledronic acid Calcitonin Raloxifene Denosumab Teriparatide

38 Drug PMO GIO Men Estrogen Calcitonin Prevention Treatment Prevention Treatment Alendronate Risedronate Ibandronate Zoledronic acid Raloxifene Denosumab Teriparatide

39 1 st line: ALN, RIS, ZOL, DMAB 2 nd line: IBN, RAL Calcitonin: last line of therapy Teriparatide: for patients with very high fracture risk Advise against the use of combination therapy Watts et al Endoc Pract 2010;16(6):1016-9

40 Monoclonal antibody that binds to and inhibits sclerostin (sclerostin inhibits bone formation). Decrease rate of vertebral, nonvertebral and hip fractures compared to alendronate. Increase cardiovascular adverse events (2.5% vs 1.9%.

41 Baseline DXA spine or total hip, repeat every Need to be done at same facility. Each Dexa scan has a Least Significant Change (LSC) Increase to longer than 2 years if stable BMD. Declined in BMD: <5% BMD continue therapy > 5% BMD switch to IV bisphosphonate or denosumab, teriparatide.

42 Used for bisphosphonates or denosumab. Bone turnover markers: - urinary N-telepeptide (NTX) - serum carboxy-terminal collagen crosslinks (CTX) Goal: decrease by 50% of NTX decrease by 30% of CTX.

43 Bisphosphonates Mild osteoporosis: stop after 4-5 yrs of stability High fx risk: drug holiday of 1-2 yrs after 10 yrs of treatment Follow BMD and bone turnover markers during a drug holiday period

44 1. Review the actual DXA to ensure there is a true loss Mistakes in interpretation can occur Must know the least significant change. 2. Adequate calcium and vitamin D True loss in a compliant patient and no secondary causes Consider a change in RX PO bisphosphonate to IV or to an agent with a different mechanism of action. 3. Evaluate for missed secondary causes

45 Compston J, Bowring C, Cooper A, et al. Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG) update Maturitas. Jun National Osteoporosis Foundation (NOF). Nof.org. International Society for Clinical Densitometry (ISCD), Feb,2014 Orlando International osteoporosis foundation (IOF) CanalisOsteoporos Int 2007;18:1319 Manologas J Bone Miner Res 1999;14:1061 Angeli Osteoporos Int 2006;39:253 van Staa Arth Rheum 2003;48:3224 Feldstein Osteoporos Int 2005;16:2168 Cohen Adi, Shane E.Primer ASBMR 2009; Grossman et al, 2010 Arthritis Care & Research;62: GIOP Recommendations, Grossman et al American Association of Oral and Maxillofacial Surgeons