Osteoporosis Update E. Michael Lewiecki, MD Director, New Mexico Clinical Research & Osteoporosis Center Director, Bone Health TeleECHO University of New Mexico Health Sciences Center Albuquerque, NM

Disclosure Institutional Grant / Research Support Consulting Speaking Amgen Consulting Amgen, Radius Speaking Radius

Objectives Assess fracture risk in geriatric patients Evaluate patients at risk for fracture Explain current osteoporosis treatment guidelines

A Brief History of Osteoporosis How did we get where we are today? E. Michael Lewiecki, MD Personal Opinion

Osteoporosis Care CRISIS Better Worse Then Now USA DXA Reimbursement Cuts (2007) WHI (2002) ONJ AFF Bureaucracy Media Reports FRAX Limited Time Fear of Side Effects Guidelines Competing Priorities More Marketing Drug Holidays Approval of More Drugs Calcium Competing Guidelines US Surgeon General’s Report Vitamin D Increasing Availability of DXA Risk Communication Bone Mass Measurement Act Treatment Gap Mass Marketing CRISIS Approval of Alendronate WHO Diagnostic Criteria DXA Introduced (1987)

US Hip Fracture Trends 2002-2015 Hip Fracture Rates DXA Medicare Payments $139 Osteoporosis Diagnosis $82 $42 DXA Testing

Will I end up like my mother? Fracture Risk Assessment Intervention Thresholds Treatment Follow-up

Indications for BMD Testing Women age ≥ 65 and men age ≥ 70 Younger postmenopausal women, perimenopausal women, and men age 50-69 based on risk factor profile Adults with fragility fracture, disease or condition associated with low BMD or bone loss Extracted from NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis and ISCD Official Positions, 2015.

Open access (free download) at www.iscd.org DXA Quality Matters Open access (free download) at www.iscd.org DXA Best Practices. Lewiecki EM et al. J Clin Densitom. 2016;19(2):127-140.

WHO Classification of BMD T-score Normal -1.0 or higher Osteopenia Between -1.0 and -2.5 Osteoporosis -2.5 or lower Severe Osteoporosis -2.5 or lower + fragility fracture Applies to postmenopausal women and men age 50 and older. Cannot be used in premenopausal women and men under age 50. Should never be used in children (under age 20). WHO Study Group 1994. ISCD Official Positions.

Caveats with WHO Classification T-score ≤ -2.5 is not always osteoporosis Example: could be osteomalacia or CKD-MBD T-score > -2.5 may be osteoporosis Example: fragility fracture, FRAX Fracture risk is determined by more than BMD Example: age, previous fracture, falls

Most Women with Hip Fracture have T-score > -2.5 Wainwright SA et al. J Clin Endocrinol Metab. 2005;90:2787-2793.

Look for Vertebral Fractures VFs are common Most VFs are not diagnosed VFs have serious consequences VFs predict future fractures Detection of VFs may change diagnostic classification, assessment of fracture risk, and clinical management* *NOF Guide: VF is indication for treatment regardless of BMD

Indications for Vertebral Imaging Women age ≥ 70 and men age ≥ 80 if T-score is ≤ −1.0 at the LS, TH, or FN Women age 65 to 69 and men age 70 to 79 if T- score is ≤ −1.5 at LS, TH, or FN Postmenopausal women and men ≥ age 50 with specific risk factors: Low-trauma fracture during adulthood (age ≥ 50) Historical height loss ≥ 1.5 in. Prospective height loss ≥ 0.8 in. Recent or ongoing long-term glucocorticoid treatment National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. 2014.

VFA = Vertebral Fracture Assessment A non-invasive method of diagnosing vertebral fractures by DXA with greater patient convenience, less cost, and lower radiation exposure than conventional X-ray

3 Ways to Diagnose Osteoporosis BMD testing (WHO, ISCD) T-score ≤ -2.5 at LS, TH, FN, or 33%R Fragility fracture (NBHA) Low trauma hip fracture regardless of BMD Low trauma vertebral, proximal humerus, pelvis or some distal forearm fractures with T-score between -1.0 and -2.5 FRAX (NBHA, USA only) MOF risk ≥ 20% or HF risk ≥ 3% WHO Technical Report. 1994; ISCD Official Positions. 2015. Siris ES et al. Osteoporos Int. 2014;25:1439-1443.

NOF Treatment Guidelines Initiate pharmacologic treatment in postmenopausal women and men age ≥ 50 when . . . T-score ≤ -2.5 or less at FN, TH, or LS, or . . . Hip or vertebral (clinical or morphometric) fracture, . . . T-score between -1.0 and -2.5 at FN, TH, or LS, and FRAX 10-year probability of hip fracture ≥ 3% or major osteoporotic fracture ≥ 20% National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. 2014.

Laboratory Evaluation CBC Blood chemistries Creatinine Calcium Phosphorus Albumin Alkaline phosphatase Liver enzymes 24-hour urine for calcium, sodium, and creatinine 25-OH-vitamin D TSH Bone turnover markers FSH Urinalysis SIFE/SPE/UPE Intact PTH Dexamethasone suppression or urinary free cortisol Bone biopsy? Low phosphorous suggests osteomalacia.

Universal Recommendations Regular weight-bearing exercise Fall prevention Avoid tobacco use and excess alcohol Identification and treatment of risk factors for fracture Calcium 1000-1200 mg/day, ideally from diet Vitamin D 800-1000 IU/day, target ≥ 30 ng/mL National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. 2014.

Medications for Osteoporosis Inhibit Bone Resorption Stimulate Bone Formation Alendronate (Fosamax, generic) Teriparatide (Forteo) Risedronate (Actonel, Atelvia, generic) Abaloparatide (Tymlos) Ibandronate (Boniva, generic) Zoledronate (Reclast, generic) Denosumab (Prolia) Raloxifene (Evista, generic) Calcitonin (Miacalcin, Fortical) Estrogen (various) CE/BZA (Duavee) Investigational compound: romosozumab (Evenity)

Individualizing Initial Treatment Agent Comments Oral BPs Pro: inexpensive, work well in many patients Con: GI distress, avoid with low GFR, bad rep in lay press ZOL Pro: very long dosing interval, post-hip fracture data Con: acute phase reaction, avoid with low GFR, IV Dmab Pro: long dosing interval, greatest BMD increase, SC Con: FDA list of “side effects” (back pain, high cholesterol, etc.) TPT Pro: anabolic Con: high cost, daily injection, refrigeration, rat osteosarcoma Abalo Pro: anabolic, no refrigeration, less hypercalcemia than TPT Con: cost, daily injection, rat osteosarcoma RLX Pro: not a BP, decreases breast cancer risk Con: VTE, hot flashes, no proven hip fracture decrease Personal opinion.

Special Issues: Efficacy Imminent fracture risk - a recent fracture imparts greater fracture risk than a remote fracture Agents with proven hip fracture risk reduction: ALN, RIS, ZOL, Dmab (not IBN, salmon calcitonin) Very high fracture risk - consider anabolic therapy (TPT, Abalo; Romo in FDA review) Convenience of dosing (nursing home, polypharmacy) - injectable therapy (ZOL, Dmab) Adherence to therapy - long acting agents may be preferable Personal opinion.

Special Issues: Safety Renal function – Limitations with BPs, not with Dmab GI (swallowing disorders, inability to remain upright, esophageal stricture, gastroparesis, bariatric surgery) – Oral BPs should not be used AFF – Consider BP holiday under appropriate circumstances (not for other drug classes) Clotting disorders – avoid ET and RLX High risk of osteosarcoma (XRT to skeleton, unexplained high alk phos, etc) – avoid TPT, Abalo Personal opinion.

Postmenopausal Women Treated with Oral BP ≥ 5 Years or IV BP ≥ 3 Years Low fracture risk Definition: hip T-score > -2.5 and no hip, spine, or multiple osteoporotic fracture before or during therapy Suggestion: consider drug holiday of 2-3 years High fracture risk Definition: hip T-score ≤ -2.5 or hip, spine, or multiple osteoporotic fracture before or during therapy Suggestion: consider continuing oral BP up to 10 years and IV BP up to 6 years Adler RA et al. J Bone Miner Res. 2016;31:16–35.

USA Participants: 21 Months Bone Health USA Participants: 21 Months 263 registered, 221 attended at least once, 35-50 attendees each week Other countries Canada Mexico Chile Brazil Trinidad and Tobago Ireland UK Register at www.ofnm.org

95 year-old woman with osteoporosis competes in powerlifting contest: curled 33 lbs, bench pressed 50 lbs, and deadlifted 82 lbs.