Osteoporosis Treatment Update:Can we Take a Holiday?

Robin Cornell Creamer, DO, FAAPMedical Director, AdventHealth Family Medicine Winter Park, Fl

Disclosure Statement

It is the policy of the AAFP that all individuals in a position to control content disclose any relationships with commercial interests upon nomination/invitation of participation. Disclosure documents are reviewed for potential conflicts of interest. If conflicts are identified, they are resolved prior to confirmation of participation. Only participants who have no conflict of interest or who agree to an identified resolution process prior to their participation were involved in this CME activity.

All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

Learning Objectives1. Evaluate elderly patients or patients at risk for low bone

mass/osteoporosis using the FRAX® algorithm and consider the impact of fracture risk scores on patient management.

2. Advise patients on appropriate prophylactic strategies for patients with low bone mass/osteoporosis.

3. Compare and contrast management with RANKL inhibitor vs bisphosphonates; and the pros and cons between various bisphosphonates.

4. Determine the risks and benefits of maintaining bisphosphonate treatment for greater than 5 years.

Osteoporosis Diagnosis and Treatment Guidelines and Educational Resources

AACE/ACE (American Assoc Clinical Endo) May 2020 ACP (American College Physicians) endorsed by AAFP: May 2017 NOF (National Osteoporosis Foundation) Clinicians Guide 2014 FRAX: http://www.shef.ac.uk/FRAX or APP University New Mexico. Telementoring Bone Health TeleECHO Clinic.

http://www.ofnm.org/project-echo Mayo Clinic Shared Decision-Making National Resource Center

https://osteoporosisdecisionaid.mayoclinic.org

Complete references in bibliography

OsteoporosisBone disease marked by reduced bone strength leading to an increased risk of fractures.

Bone Strength = Bone Mass (density) + Bone Quality (microarchitecture)

Normal Bone Osteoporotic Bone

Impact of Osteoporotic Fractures

80% CARE GAP

Over age 50 upto

½ women

¼ men

will break bonedue to osteoporosis

After a fracture, Only 1/5

women over 67are tested or treated for

osteoporosis

Osteoporotic fractures

will likely cost us

$25billion

per year by 2025

300,000 hip fx/yr

¼ will die within a year

¼ end up in nursing homes &

½ will need a walking aid

Vertebral Compression Fractures (VCF)Most common osteoporotic fracturesWedge fractures most common VCF T7-T8; T12-L1 most common sites 75% are not clinically evidentPatients with a spine fracture have a

5-fold future risk of a spine fracture and 2-fold risk of a hip fracturePulmonary: 9% decrease in lung capacity

per vertebral fractureGI: Constipation, early satiety, wt loss,Psychosocial: depression, social isolaton

Strong Bones Begin in Childhood

DXA Screening Recommendations

USPSTF 2018: All women ≥ 65 y (B rec.) Younger postmenopausal women at increased risk as determined by a

formal clinical risk assessment tool. (B rec.) Men: Evidence is insufficient to recommend screening in men to prevent

osteoporotic fractures. (I statement) Note: NOF recommends screening men ≥ 70 y and younger men with risk factors, ie:

fracture after 50 y, steroids, et al.

NCQA HEDIS measure: Number of women ≥ 65 who report ever having a BMD test.

www.shef.ac.uk/FRAX

Updated FRAX ® Risk estimate65 yo WF w/o major risk factors in U.S.8.4% MOF(BMI 28.8) instead of 9.3% (BMI 25)

Risk Assessment Tools in addition to FRAX (1 of 2)Tool Risk Factors Scoring Threshold for

Increased RiskOST(OsteoporosisSelf-Assessment Tool)

Weight (kg)Age (y)

kg- y < 10

ORAI(OsteoporosisRisk Assessment Instrument)

Age,y ≥ 75 y 65-7455-6445-54

Wt, kg < 60 kg 60-69≥ 70

No current estrogen use

15950930

2

≥ 9

Risk Assessment Tools in addition to FRAX (2 of 2)Tool Risk Factors Scoring Threshold for

Increased Risk

OSIRIS(Osteoporosis Index of Risk)

Age, yWeight, KgCurrent estrogen usePrior low-impact fracture

-0.2 x age0.2 x kg2-2

< 1

SCORE(Simple CalculatedOsteoporosis Risk Estimation)

Non-black raceRheumatoid arthritisPrior non-traumatic rib/wrist/hip fx after age 45

Never used estrogenAge, yWt, lb

54

4 for each (max 12)13 x 1st digit of age-1 x (lbs / 10)

≥ 6

AES Question

In which of the examples below is DXA testing not indicated?

A. 66 yo male with history a non-traumatic fractureB. 75 yo female with normal DXA scan 2 yrs ago, without risk

factors for osteoporosis.C. 80 yo female who has been on oral bisphosphonate for 5

yrs. D. 90 yo female who has not had a baseline DXA scan

Question 1

WHO Diagnosis of Osteoporosis

T- score

Normal Equal to -1.0 or higher

Low Bone Mass (Osteopenia) Between -1.0 and -2.5

Osteoporosis Equal to -2.5 or lower

Severe Osteoporosis Equal to -2.5 or lower with fracture

1. Bone Mineral Density as defined or2. Fragility fracture of hip or spine

NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis.2014

T-score -2.5 or below Lumbar spine, femoral neck, total proximal femur, or 1/3 radius

Low-trauma spine orHip fracture Regardless of bone mineral density

T-score between -1.0 and -2.5 Fragility fracture of proximal humerus, pelvis, or distal forearm

T-score between -1.0 and -2.5 High FRAX ® (or if available, TBS adjusted FRAX®) fracture probability based on country-specific thresholds.

2020 AACE/ACE Diagnostic Criteria for Osteoporosis in Postmenopausal Women(PMW)

FRAX adjusted with Trabecular Bone Score (TBS)FDA approved in 2012, TBS is a Textural index: DXA software

that extracts bone texture information from an AP spine DXA scan imageShown to be related to bone microarchitecture and fracture riskProvides information independent of BMDCannot diagnose osteoporosisCan be used to improve fracture risk assessment

.Siris. Arch Intern Med. 2004;164(10):1108-1112.

Most Factures in Postmenopausal Women Occur WithT scores in Low Bone Density (Osteopenic) Range

NOF Recommendation for Vertebral Fracture Imaging Assessment

Consider Vertebral Imaging tests for the following:Women ≥ 70 y and Men ≥ 80 y, if BMD T-score spine, total hip or femoral neck is < -1.0.

Women 65-69 y and men 70-79 y,if BMD T-score spine, total hip or femoral neck is < -1.5

Postmenopausal women and men age 50 and older with specific risk factors: • Low trauma fracture ≥ 50 y• Historical height loss ≥ 1.5 inches (4 cm)• Interval height loss ≥ 0.8 inches (2 cm)• Glucocorticoid use

NOF Guidelines for Rx TreatmentFactor Description

Fracture Hip or SpineT-score (DXA) T-score ≤ -2.5 at spine,

hip or femoral neckFRAX (osteopenia,low bone mass)

10-year probability of amajor fracture (MOF) ≥ 20%10-year probability of a hip fracture ≥ 3%

National Osteoporosis Foundation’sClinician’s Guide to the Prevention and Treatment of Osteoporosis. 2014

Most common undiagnosed disorders of bone and mineral metabolismHypercalciuriaMalabsorption of calciumHyperparathyroidismVitamin D DeficiencyHyperthyroidismCushing’s disease

Labs to Consider for Secondary Causes

Chemistry (calcium,renal, phosphorus) Liver function testsCBC TSH, iPTH 25(OH)Vitamin D Testosterone younger men 24-hour urine calcium, Na, creatinine

Selected cases:SPEP/UPEPCeliac disease-(tTG) Iron and ferritinHomocysteine TryptaseProlactinBone turnover markers

Advise Universal Recommendations for Bone Health Regardless of Bone DensityAdvise adequate dietary calcium intake, supplement if diet is

insufficient Advise adequate Vitamin D intake, supplement if diet is

insufficientSmoking cessation. Limit alcohol and caffeine consumptionRecommend exercise program for strength, posture and

balance Fall Prevention

AES Question

Which of the following is true?

A. Advise patients with osteoporosis to consume more calcium than patients with normal bone density.

B. Advise patients with osteoporosis to consume more vitamin D than patients with normal bone density.

C. Advise patients with osteoporosis to avoid spinal forward flexion exercises.

D. Advise patients with osteoporosis to avoid spinal extension exercises

Question 2

Institute of Medicine: Dietary Reference Intakes for Calcium and Vitamin D -- 2011

YEARS CALCIUM (mg/d)Recommended Dietary Allowance

VITAMIN D (IU/d)Recommended Dietary Allowance

19-50 y M/F 1,000 600

51-70 y Males 1,000 600

51-70 y Females 1,200 600

>70 y M/F 1,200 800

Vitamin D replenishment and Supplementation

If serum 25[OH]D 20 to 29 or < 20, replenish with Vitamin D 5,000 IU daily for 8-12 wks to achieve level ≥ 30

Sturdy study- falls in community dwelling ≥ 70 yrs 200 & 1,000 iu/ day fewer falls than 2,000 or 4,000 iu/ day

groupNo benefit from higher doses

Appel,L; Michols,E, et al. The Effects of Four doses of Vitamin D Supplements on Falls in Older Adutls. Ann Intern Med. 2021;174:145–156.

Too Fit To Fracture RecommendationsFor preventing bone loss and falls, recommend a combination of: Strength training for major muscle groups ≥ 2x/week Balance challenges daily Moderate-to-vigorous aerobic physical activity ≥ 150 min/week, or 20-

30 min per dayTo reduce spine loads, recommend: Exercises for back extensor muscles daily Spine sparing strategies – hip hinge for bending, step-to-turn instead of

twisting, holding loads close to body

Giangregorio LM, et al Osteoporos Int. 2014

https://cdn.nof.org/wp-content/uploads/2016/05/Safe-Yoga-NOF-Flyer-2016.pdf

Physical Therapy for Bone Health

Physical TherapyMedicare accepts Physical Therapy ICD 10 diagnosis code of

Osteopenia (M85.80) or Osteoporosis (M81.0) • 1-3 sessions usually all that is needed for osteopenia to

review posture and exercise routine.Rx: Osteoporosis/ Osteopenia: Physical Therapy to evaluate,

treat and instruct in spine safe posture and exercise to optimize strength and balance. Minimize fall risk.

• VCF- decreases risk of subsequent VCF’s

AAFP Endorsed 2017 - ACP Guideline Update:Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women

1. Treat with alendronate, risedronate, zoledronic acid or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis(grade: strong rec; high-quality evidence)

2. Treat osteoporotic women with pharmacological therapy for 5 years.(Grade:weak rec; low-quality evidence)

3. Treat with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis.(Grade: weak rec:low-quality evidence)

AAFP Endorsed 2017 - ACP recommendations cont.

4. Against bone density monitoring during the 5-yr period pharmacologic treatment period for osteoporosis in women. (Grade:weak rec; low quality evidence).

5. Against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women.(Grade:strong rec; mod-quality evidence).

6. Treat osteopenic women 65 yrs age and older who are at a high risk for fracture based on a discussion of pt preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade:weak rec.;low-quality evidence)

Pharmacology• Antiresorptive

Bisphosphonates• Alendronate (Fosamax)• Ibandronate (Boniva)• Risedronate (Actonel)• Zoledronic Acid (Reclast)

Denosumab (Prolia)Raloxifene (Evista)EstrogenCalcitonin

Anabolic (Bone Forming)Teriparatide (Forteo)Abaloparatide (Tymlos)Rozosumab (Evenity)

Fracture Data PostmenopausalMEDICATION SPINE HIP NON-VERT DOSE/ADMIN

BisphosphonatesAlendronate(Fosamax)

✓ ✓ ✓ 70 mg po weekly

Ibandronate(Boniva)

✓ 150 mg po monthly3 mg IV every 3 mo.

Risedronate(Actonel, Atelvia)

✓ ✓ ✓ 35 mg po weekly150 mg po monthly

Zoledronic Acid(Reclast)

✓ ✓ ✓ 5 mg IV yearly

MEDICATION SPINE HIP NON-VERT DOSE/ADMIN

Denosumab (Prolia) ✓ ✓ ✓ 60 mg SC every 6month

SERM-Raloxifene(Evista)

✓ Not recommended due to adverse effects

Estrogen ✓ ✓ ✓ Not recommended due to adverse effects

Calcitonin(Miacalcin,Fortical)

✓ Not recommended due to adverse effects

Teriparatide(Forteo)

✓ ✓ 20 mcg SC daily for max 2 yrs

Abaloparatide(Tymlos)

✓ ✓ 80 mcg SC daily for max 2 yrs

Romosozumab(Evenity)

✓ ✓ ✓ 2 injections monthly x 12 mo.

Bisphosphonates (BP)

• PMW, men, steroid induced osteoporosis• Fx Reduction RR in Postmenopausal women from RCTs:

Spine ~50% alendronate, risedronate, zoledronic acid & ibandronate

Hip ~ 40% with all except ibandronate• Short term (3-5 yrs) benefits far exceed risks• Long term (>5 yrs) benefits smaller, risks higher• Oral alendronate first line due to efficacy, safety data, cost $7/month.• Specific dosing regime due to adverse effects of esophagitis• IV-Zoledronic acid, if unable to follow oral dosing or GI intol• Caution: CrCl <35; Hypocalcemia-monitor Ca, Mg, PO4

AFF: Associated with long-term use >5 yrs. Evaluate for Drug holiday after 5 yrs of treatmentRare <0.1% or absolute risk 5 cases/10,000 pt tx yrsInquire about thigh or groin painEvaluate any pain for stress fracture with bil femur x-rays

ONJ: Rare 1/10,000 to 1/100,000 riskConsider dental exam prior to startingRecommend good oral hygiene

Atypical Femoral Fractures(AFF) & Osteonecrosis of Jaw (ONJ)Rare serious adverse effects: Bisphosphonates

Used with permission from Victor Montori,M.D., Mayo Clinic

Mayo Shared Decision Aid https://osteoporosisdecisionaid.mayoclinic.org

Communicating RisksMotor Vehicle Accidents

0

25

50

75

100

Injuries &Deaths

WearingSeat Belt

Seat BeltInjuries

Osteoporosis

0.

25.

50.

75.

100.

FracturesUntreated

FracturesTreated

ONJ +AFF

Wearing seat belts reduces the risk of serious crash-related injuries and deaths by about 50%

Treatment with bisphosphonates reduces the risk of fractures by about 50%

There are about 2.3 million adults treated in ERs each year for injuries from MVAs and about 2 million osteoporotic fractures each year. The risk of seat belt injuries and serious side effects from osteoporosis treatment is very small in proportion to the benefits. Data from multiple sources.

Used with permission from Michael Lewiecki,MD

AES Question

A. After treatment with an oral bisphosphonate for 5 yrsB. After treatment with IV bisphosphonate (zoledronic acid) for

3 yrsC. After treatment with denosumab for 5 yrsD. After treatment with teriparatide for 2 yrsE. A and B

Question 3

In which scenario is it appropriate to consider a Drug Holiday?

Time for a Bisphosphonate (BPs) Drug Holiday?

Risk of AFF, but not ONJ, increases with BP therapy > 5yrBMD increase for upto 3 yrs, no further gain thereafter. No further reduction in fx risk beyond 3-5 yrsRetained in skeleton with long half life, Residual effect after discontinuationZoledronic acid- longest residual effectRisedronate- shortest

Consider drug holiday, after 5 yr of oral BP or3 yr of IV BP( Zolendronate)

Evaluate with DXA and Vertebral Fracture Assessment (VFA)

Time for a Bisphosphonate Holiday?

Consider a Drug Holiday if fracture risk is no longer high: T-score greater than -2.5Patient has remained fracture freeRepeat DXA after 2 yrs of holiday

Patients remaining high risk, continue oral BP additional 5 yrs(up to 10 yrs) and up to 6 yrs for IV BP(Zoledronate) before drug holiday

AES Question

Which is NOT correct regarding a drug holiday?

A. “Holiday” is a bisphosphonate(BP) specific concept, not appropriate for denosumab or other non-bisphosphonate drugs

B. Consider drug holiday after 5yr oral BPs or 3yrs IV BPs. Patients who remain high fracture risk, consider continuing oral BPs up to 10yr and IV BPs up to 6yr.

C. It not recommended to check a DXA again for patients on BPs Drug Holiday

D. If denosumab is discontinued, patients should be transitioned to a bisphosphonate to lower risk of discontinuation vertebral fractures

Question 4

BPs Drug Holiday ≠ Drug Retirement

During BPs drug holiday, assess need to resume treatment every 2-4y with DXA. Fracture risk starts to increase about 2 yrs after

stopping BPs.Risk of AFF resolves quickly (1 yr) Resume therapy whenA fracture occursPatient meets initial treatment criteria

What if there is progression of bone loss or fracture while on oral Bisphosphonate?

Assess complianceRe-evaluate for causes of secondary osteoporosisSwitch to injectable anti-resorptive(zolendronate or

denosumab) if on oral agent

Roles for Bisphosphonates

Initial treatment for osteoporosisLast treatment for anabolic treatment sequence to

maintain the benefitsTreatment after denosumab withdrawal to lower risk of

discontinuation vertebral compression fractures. Long-term maintenance of BMD, sequence on and off

BPs.

Denosumab –DMab (Prolia) Monoclonal antibody, RANKL inhibitor, approved for PMW and men. Approved for cancer induced bone loss from hormone ablation tx. Administer: SQ inj 60 mg every 6 mo.; Cost $1,000/ inj Freedom Trial: reduces vertebral, non-vertebral, and hip fractures Freedom Ext study 10y low rate of adverse events, fracture risk

further reduced and continued BMD gains with longer term therapy Caution: If risk of hypocalcemia, CrCl < 30, check calcium 10d after

injection. Adverse: Infection skin. Rare complications include AFF and ONJ Delayed dose or discontinuation is associated with Multiple

Vertebral Fractures and rapid loss of BMD. Reasonable initial therapy in those with life expectancy <10 yr Transition to BPs to avoid fractures is complicated.

Transition off Denosumab –DMab (Prolia)Vertebral fractures occurred as early as 2 month delay (8 months

from last inj). Do not stop DMab w/o transition to a BPsAlendronate has been shown to maintain BMD and decrease

vertebral fractures after Dmab.Alendronate can be initiated 6 months after last Dmab dose

minimum of 1-2 yrs, then consider bisphosphonate drug holiday. IV Zoledronic Acid(ZA) likely effective but timing uncertain,

possibly 7 months after last Prolia when bone turnover increases.One expert measures serum CTX monthly beginning seven

months after the last Dmab inj and administers IV ZA once CTX is at the upper limit of the ref range for premenopausal women (eg, >600 pg/mL in an assay with ref range 93 to 630 pg/mL).

Estrogen with or without Progestin; or RaloxifeneRecommend AGAINST for treatment of osteoporosis in women. ACP Grade: strong recommendation against Increased risk of stroke and thromboembolic eventsConsider Raloxifene if independent need for breast cancer

prophylaxis

Estrogen + Bazedoxifene = (Duavee) FDA indication for prevention of osteoporosisNo RCT with primary fracture outcomes

Calcitonin FDA-approved for PMW when alternative treatments are not

suitable. Reduces vertebral fractures 30% in those with prior vertebral

fractures. Not been shown to reduce non-vertebral or hip fractures.Administer: 200 IU intranasal spray. SQ availableAdverse effects: suggested increased risk of malignancies

Risk Stratification-AACE 2020 updateVery High Fracture RiskChoice of initial agent to include anabolic meds in pts with:

Advanced age; frailty; increased fall risk Fractures-

Recent <12 months; multiple or while on therapy; Glucocorticoids T score <-3.0High fracture probability by FRAX

Anabolic Therapy: PTH1 Receptor ligandsTeriparatide(PTH 1-34) and Abaloparatide (PTHrP)

Teriparatide (Forteo) and Abaloparatide (Tymlos) PMW high risk for fracture (h/o of fx or multiple risk factors) or who have

failed/intolerant to other therapies. Reduce vertebral and non-vertebral fractures; not hip Daily SQ injection. Cost estimate: $1,500 to 3,000/ month Limited to 2 years in lifetime Contraindicated: in patients with increased risk of osteosarcoma

Paget’s disease, prior radiation therapy skeleton, bone metastases, hypercalcemia, or a history of skeletal malignancy

Teriparatide- also indicated for men at high fx risk; steroid induced OPAbaloparatide- lower incidence of hypercalcemia, no need to refrigerate

Romosozumab “Evenity”

Monoclonal AB to sclerostin; FDA approved April 2019 Indication: PMW at high risk 2 Injections monthly x 12 months Primarily anabolic Follow by an antiresorptive Serious Reactions: MI, CVA, CV death, hypcalcemia, ONJ, AFF Should not be used if MI, CVA in previous yr

Sequencing of Anabolic and Antiresorptive Therapies Lifelong treatment with sequencing of medications and holidays. Only BPs safely precede holidays. Anabolic agents shown to have greater BMD gains when used

prior to an antiresorptive agent. Consider anabolic agents as initial tx in VERY high risk patientsAnabolic response may be blunted for a period of time after BPs Follow 2 yr anabolic therapy with antiresorptive (BPs or DMab) to

maintain BMD gains.Do not transition to anabolic after Dmab due to increased fx risk.

Interval Care for During Treatment Patients taking medications need to be evaluated annually Calcium, diet, exercise, lifestyle, new meds or chronic diseases Inquire if any thigh or groin pain Exam: height. 2 cm (0.8 in) loss, repeat VFA. Labs: creatinine, calcium, Mg, Vit D

DXA interval BMD testing during treatment- no RCT ACP- recommends against testing during 5 yr treatment.

- Reduced fractures with treatment even if BMD did not increase NOF: recommends every 2 yrs ISCD: If stable or increased, repeat at 5 years. If BMD decrease ≥ 5% Inquire about non-compliance; assess for secondary causes. If poor absorption of oral BP, consider switch to IV bisphosphonate

Healthy Bones for Life: Primary PreventionNCQA HEDIS measure: Number of women ≥ 65 yrs who report ever

having a BMD test. Repeat DXA interval depends on initial BMD. If no risk factors:

- Normal DXA T score >-1.49, repeat 10-15 yrs or more- T score -1.50 to -1.99, repeat in 3-5 years- T score -2.0 or less, repeat in 2 years

Patient education is the foundation of care Provide referral to Physical Therapy, Registered Dietician Consider utilizing CPT code 99490 Chronic Care Management Consider starting an NOF Support Group / Lecture Series

Improving Bone Health after a FractureNCQA HEDIS measure: Number of women ≥ 65-85 yrs who

suffered a fracture and who had either BMD or a prescription for a drug to treat osteoporosis. In adults ≥ 50 y, after a fracture, assess FRAX for DXACare coordination programs after fractureNOF- Fracture Liaison Bone Health TeleECHOAmerican Orthopedic Assoc.: Own the Bone International Osteo Foundation: Capture the Fracture

USPSTF Recommendations 2018Fall prevention in community-dwelling ≥ 65 y

Exercise intervention to prevent falls (B recommendation)Multifactorial interventions to prevent falls (C recommendation) medications, medical conditions, environmental hazards ie: CDC STEADI Program

Vitamin D supplementation not recommended (D recommendation)

These apply to community-dwelling adults NOT known to have osteoporosis or Vitamin D insufficiency or deficiency.

Practice RecommendationsActively counsel patients on the prevention of osteoporosisUse a Formal Risk Assessment Tool to identify patients for

screening and treatment of osteoporosisOsteoporosis treatment should be individualized with long-term

strategies discussed with the patient.Consider oral bisphosphonates as first line for appropriate patientsEvaluate for bisphosphonate drug holidays with DXA and VFACounsel patients on denosumab discontinuation risk & strategies. Encourage patients to exercise to decrease their fracture and fall

risk.

Questions?

Advent Health Family Medicine Residency and Geriatric Medicine

Fellowship

Robin Creamer, DO, CAQGM, FAAFPRobin.Creamer.DO@AdventHealth.org

133 Benmore Dr, Suite 200Winter Park, FL 32792Office: 407-646-7757Fax: 407-646-7775

References Adler RA, El-Hajj Fuleihan G, et al. Managing Osteoporosis in Patients on Long-Term

Bisphosphonate Treatment:Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016 Jan;31(1):16-35. Appel,L; Michols,E, et al. The Effects of Four doses of Vitamin D Supplements on Falls in

Older Adutls. Ann Intern Med. 2021;174:145–156 Black DM, Schwartz AV, Ensrud KE et al (2006) Effects of continuing or stopping alendronate

after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296(24):2927–2938 Camacho,P, et al. AACE/ACE Clinical Practice Guidelines for the Diagnosis and Treatment of

Postmenopausal Osteoporosis-2020 update. https://doi.org/10.4158/GL-2020-0524SUPPL Cosman F, de Beur SJ,et al. Clinician’s Guide to Prevention and Treatment of Osteoporosis.

Osteoporosis International. 2014;25:2359-81. PMID 25182228 Ethel S. Siris; et al. Bone Mineral Density Thresholds for Pharmacological Intervention to

Prevent Fractures. Arch Intern Med. 2004;164(10):1108-1112.

References Giangregorio,LM,et al. "Too Fit To Fracture: exercise recommendations for individuals with

osteoporosis or osteoporotic vertebral fracture." Osteoporosis International 25.3 (2014): 821-835. Kanis JA, on behalf of the World Health Organization Scientific Group. Assessment of

osteoporosis at the primary health care level. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield 2007. Mayo Clinic Shared Decision Making National Resource Center.

http://shareddecisions.mayoclinic.org/decision-aid-information McClung MR, et al (2017) Observations following discontinuation of long-term denosumab

therapy. Osteoporo Int 28:1723-1732 National Committee for Quality Assurance. HEDIS & Performance Measurement.

www.ncqa.org/HEDISQualityMeasurement.aspx National Institute of Health. National Osteoporosis Foundation(NOF) www.nof.org Office of the Surgeon General (US) (2004) Bone health and osteoporosis: a report of the

Surgeon General. Office of the Surgeon General (US), Rockville (MD). Available from: http://www.ncbi.nlm.nih.gov/books/NBK45513

References Qaseem A, et al; Treatment of low bone density or osteoporosis to prevent fractures in

men and women : a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017 Jun 6;166(11):818-839. PMID: 28492856 Shepstone L, et al; SCOOP Study Team. Screening in the community to reduce fractures

in older women (SCOOP). Lancet. 2018:391(10122):741-747. doi:10.1016/50140-6736(17)32640-5. U.S. Preventive Services Task Force. Interventions to Prevent Falls in Community-

Dwelling Older Adults. JAMA. 2018;319(16):1696-1704. doi:10.1001/jama.2018.3097 U.S. Preventive Services Task Force. Vit D, calcium or combined supplementation for

Primary Prevention of Fractures in Community-dwelling Adults. JAMA. 2018;319(15):1592-1599. doi:10.1001/jama.2018.3185 U.S. Preventive Services Task Force. Screening for Osteoporosis: U.S. Preventive

Services Task Force recommendation statement. JAMA. 2018;319(24):2521-2531.doi:10.1001/jama2018.7498

Answers

1. B2. C3. E4. C