Disclosures CLINICAL DECISION-MAKING: CASE STUDIES Radius - - - PowerPoint PPT Presentation

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CLINICAL DECISION-MAKING: CASE STUDIES

Dolores Shoback, MD Professor of Medicine, UCSF

Osteoporosis 2018: New Insights in Research, Diagnosis, and Clinical Care July 13, 2018

Disclosures

• Radius - Consulting

Selecting Treatment - Individual Patient*

• How high is the risk for that individual (clinical history

+ FRAX) ?

• What efficacy – trying to achieve ?
• What risk reduction for which type of fracture is

needed ?

• Where am I in the timing of treatment for this patient ?

What have they tried? How long? How did they do?

• Have I considered (any/all) secondary contributors ?
• How does the AE profile of the agent match the

patient – OK ?

 Optimize chances that patient accepts the treatment and complies with it

*values and preferences

Consider Doing Vertebral Imaging – NOF 2014 Guidelines

• Women 70 yrs or > and men 80 yrs or > – if the T-score is < -1.0 (LS, TH,
• r FN)
• Women 65-69 yrs and men 70-79 yrs – if T-score is < -1.5 (LS, TH, or FN)
• Postmenopausal women and men (age > 50 yrs) with specific risk factors:

– Low trauma fracture as adult (age 50+) – Historical height loss of 1.5 in or > (4 cm)

• Defined as difference between current height and peak height

(age 20) – Prospective height loss of 0.8 in or > (2 cm)

• Defined as difference between current and previously documented

heights – Recent or ongoing long-term glucocorticoids

• If DXA not avail, then vert imaging may be considered based on age alone
• If stopping therapy (as it could modify that decision)

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Considerations – New Starts

Anti-resorptive

• Bisphosphonate
• Denosumab
• Raloxifene
• (Duavee-

CE/Basodoxifene)

• ET/HT (younger)

Anabolic – teriparatide abaloparatide eGFR Active dental issues Infectious risk (skin, GU) Hypocalcemia risk Breast ca, CVD, clot risks Concomitant meds Costs ($$$) Contraindications Daily injection hurdle Patient values and preferences

Considerations: Treatment – Experienced Patient

• Try to establish the kind and duration of prior

therapy (very hard)

• Try to establish response – collect all DXA

reports, analyze along with treatment history (also hard)

• Assess compliance – you may get some

surprising results (easier than you think)

• Check fracture history
• Consider 2o workup (surprising what might

have been missed  celiac disease, hypercalciuria, Ca malabsorption etc) 56 yo woman referred by Gyn for second

• pinion – skeletal health in 2018
• Menarche age 11, regular cycles, 1 FT pregnancy,

menopause age 52; no h/o OCPs, depo-Provera

• ~Age 33 - thought to have rib fractures (after hug)
• H/O - ‘joint pains’ and +ANA, treated for 1 year with

prednisone (20 mg/d – highest; tapered off in 2017)

– Prescribed HT (refused), alendronate (never took)

• Meds: Ca suppl, vit D3 2000 IU/D
• ROS: heavy bleeding (fibroids, 5 by U/S), +several

breast biopsies (all neg), MV prolapse

• FH: father with hip fracture (Parkinson’s disease)
• Habits: no smoking or alcohol; minimal exercise, low

dietary Ca

Case 1

• Exam: 5 feet, 98 lbs; nl VS, + systolic murmur
• LAB: CBC – wnl, CMP (Ca, creat, LFTs) – wnl; 25 OH

vitamin D 53 ng/ml, TSH 1.52 L-spine L fem neck L total hip 2016 0.769 0.778 0.713

(age 54)

• 3.4
• 1.9
• 2.3

2018++ 0.561 0.555 0.604

(age 56)

• 4.4
• 2.7
• 2.8

(++different lab)

FRAX* 19% 10-yr risk of major osteoporotic frx, 2.3% 10-yr risk of hip frx (20%, 3% - US thresholds)

Case 1 – cont’d

*Parental hip frx, steroids

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Postmenopausal + glucocorticoid osteoporosis

• Complete workup: anti-tissue transglutaminase Ab, 24

hr urine Ca, PTH, T/L spine films (r/o occult frx) Management

• Optimize Ca intake (vit D3-ok), start wt bearing

exercise (5/7 days per week)

• Despite FRAX not meeting US thresholds (spine xrays

neg)  offer pharmacologic therapy ?

– Hormone therapy – Raloxifene – Bazedoxifene+CE (Duavee) – Bisphosphonate – Denosumab – Teriparatide – Abaloparatide

Approach to Management

*

• HT (ET, EPT) – most effective for vasomotor

symptoms and GU syndrome of menopause, prevents bone loss and fracture

• Treatment – individualized (type, dose, routes,

duration) to maximize benefits and reduce risk, with periodic re-evaluation of risks and benefits

• Women < 60 yrs old or within 10 yrs of menopause

– If no contraindications, benefit/risk ratio – good, esp if +vasomotor symptoms and at high risk for bone loss or fractures (this pt no VMS)

• Women > 60 yrs old or >10 yrs postmenopause

– Risks higher for CV disease, stroke, VTE, dementia (not endorsing in these women)

Continue therapy if documented indication (“silent”

• n duration  “individualize”)

North American Menopause Society: Position Statement (Menopause, 24, 728, 2017) Age and Adverse Event Profile: HT

NAMS Position Statement, Menopause, 24, 728, 2017

– Agreed to more calcium (1,200 mg/d), exercise My choice Her choice Hormone therapy * Raloxifene XXX Bazedoxifene + CE* Bisphosphonate #2 Denosumab Teriparatide #1 Abaloparatide #1

* fibroids, breast disease (Gyn rec against any form of HT)

 Individualized management, shared decision-making

Management

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56 yo woman referred by Women’s Health Clinic for management of low BMD in 2015

• Menarche age 12, regular cycles, menopause age 51;

no OCPs, depo-Provera, glucocorticoids

• Fell on ice (age 48) – living in NJ  tibial frx
• PMH: + duodenal ulcer (2 unit-UGI bleed in 2015); h/o

gastric ulcer; + hyperlipidemia; +HTN

• Meds: HCTZ 12.5 mg, Simva 20 mg, Omeprazole 20

mg bid, occas MVI

• ROS: +sciatica (back pain; shooting pains in both

legs)

• FH: +osteoporosis in mother (wheelchair late in life)
• Habits: + smoking (40 pack-years), occ social drinker;

active at work (small business owner0, but limited exercise; low dietary Ca

Case 2

• Exam: 115 lbs, BMI 21.4; nl VS and exam
• LAB: CBC – wnl, CMP (Ca, creat, LFTs) – wnl; 25 OH

vitamin D 21 ng/ml; TSH 1.61; 24 h urine Ca 70 mg (100-250); PTH 36 (15-88); SPEP nl L-spine L fem neck L total hip 2/2015 0.706 0.637 0.746

(age 56)

• 3.1
• 1.9
• 1.6

Spine xrays: disc space narrowing (L4-5, L5-S1, no frx) CT: mod DDD, disc bulges @ multiple levels, no frx FRAX (2015)*: 13% 10-yr risk of major osteoporotic frx, 2.5% 10-yr risk of hip frx (20%, 3% - US thresholds)

Case 2 – cont’d

* Counting fall on ice (age 48)

Postmenopausal osteoporosis – evident at age 56

(+FH, smoking, petite body habitus, low Ca intake, +/-vit D)

• Complete workup: anti-tissue transglutaminase Ab

Management

• Optimize Ca and vit D3 intake (1200 mg, 2000 IU/d),

start wt bearing exercise (5/7 days per week), reduce lifting at work, STOP smoking

• FRAX - does not meet US thresholds  offer

pharmacologic therapy ?? (spine T score -3.1)

Approach to Management

Postmenopausal osteoporosis – evident at age 56

(+FH, smoking, petite body habitus, low Ca intake, +/-vit D)

• Complete workup: anti-tissue transglutaminase Ab

Management

• Optimize Ca and vit D3 intake (1200 mg, 2000 IU/d),

start wt bearing exercise (5/7 days per week), reduce lifting at work, STOP smoking

• FRAX - does not meet US thresholds  offer

pharmacologic therapy ?? (spine T score -3.1)

– Hormone therapy * smoking concern – Raloxifene – Bazedoxifene+CE (Duavee) * smoking concern – Bisphosphonate *** oral – no d/t GI bleed, ulcers – Denosumab – Teriparatide ** refused daily injections, missed 2 f/u appt’s

Approach to Management

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Tissue Selective Estrogen Complex (CE + SERM Bazedoxifene)

• Conjugated estrogen + bazedoxifene 20 mg
• Like estrogen – “boxed warning”  women over age

65 – increased risk of dementia, endometrial cancer, stroke, DVT

• This combination – no increased risk for endometrial

hyperplasia; insufficient data to evaluate risk for CV events (no progestin)

• Contraindications: uterine bleeding, breast ca,

arterial/venous TEE’s, liver disease, thromophilic disease

• AE’s (RCTs): decently tolerated, less vaginal

bleeding vs CE (H2H trials)

Gallagher JC et al, Menopause, 2016

• 1172 pm women, mean age 54.9 years, FRAX score

5% or less   “protective”

BMD Responses to TSEC vs PBO (12 mon)

• 7 year study (2 extensions)
• 7492 women, age 55-85

yrs (average 66-67)

• Osteoporotic at baseline

(BMD, prevalent vert frx)

• Reduction in vert frx 42%

and 37% (BZA 20 vs 40 mg/d) – no effects on nonvert frx (3 years rx)

Palacios S et al, Menopause, 2015

7 years

Lumbar spine Total hip

• Opted for IV zoledronic acid (compliance, avoid PO)
• Received in 2/2016 and 2/2017 (5 mg)
• Interval history (6/2018): inferior wall STEMI –

requiring 4 stents in 4/2017; d/c smoking completely L-spine L fem neck L total hip 2/2015 0.706 0.637 0.746

(age 56)

• 3.1
• 1.9
• 1.6

6/2018 0.767 0.652 0.761

(age 59)

• 2.5
• 1.8
• 1.5

% change +8.6% +2.4% +2.0% Management now: Post-STEMI (no enthusiasm for estrogen-based therapy); at spine, + changes exceed least significant change (so real)

Case 2 – cont’d

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Management of patients on long-term bisphosphonates (Adler RA et al, JBMR, 2016)

 Give another year of IV ZOL (currently 5 months late); likely “drug holiday” (age 60 yrs)

Case 3

57 yo Caucasian woman ref by Hospital Medicine Service after adm for osteoporosis and severe back pain

Present Illness:

• On way to work, she leaned forward (about 5o) and

heard a “loud pop”, followed by immediate, severe back pain ~waist level (10/10, sharp) radiating down both legs to her feet.

• Within 2 days: presented to Screening Clinic for
• ngoing pain and muscle spasms. Treated with

flexeril, some relief. No motor or sensory complaints

• r incontinence.
• 3 days later: unable to work, presented to ER,

admitted for incapacitating pain. Xrays  compression fracture of L1.

Case 3 – cont’d

• Menses (age 12); one FT pregnancy; no eating

disorders, depo-provera or significant steroid use

• Menopause (age 50/51) with intense ’hot flashes’

– still daily. No ET, treated Lexapro initially (no relief), switched to Bupropion (+/- relief)

• Family history: + osteoporosis in mother and

father (no hip frx)

• Fractures: age 53 - fell over coffee table  “rib

fractures” (+xray), same year had ‘rib fracture’ after being hugged.

• DXA (age 53)  ”osteoporosis”; started weekly

alendronate 70 mg, daily Ca and vit D3 supplements (says 100% compliant)

Case 3 – cont’d

• Meds

Miacalcin NS daily, Ca 500 mg/vit D3 125 IU bid, Aln 70 mg/wk, ibuprofen 800 mg tid, cyclobenzaprine 5 mg, acetaminophen 1000 mg tid, bupropion 150 mg qd

• Exam VS – WNL 5’ 7” Wt 136 lbs. In

pain, wearing thoracic brace; spine diffusely tender with guarding, unable to lean forward without pain or lie flat. No stigmata of 2o osteoporosis; neurologically - intact to motor and sensory testing, slow gait

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Xray - Lumbar Spine

• L1 compression

fracture (50 to 60% height loss)

• Mild osseous

retropulsion

• T7 compression

fracture (~40% height loss)

• Both were age-

indeterminate

CT Scan – L1 frx T2-weighted, fat-suppressed MRI Acute L1 comp frx; 40% height loss assoc w/superior endplate, 1 cm bony retropulsion; moderate bony canal stenosis; NO lytic or sclerotic bone lesions L1 frx w/retropulsion with effacement of the ventral CSF space, mild canal narrowing; no abnl cord signal, cord compr or epidural hematoma

Case 3

LABS: Chem panel, CBC, SPEP, UPEP, quant Ig’s, liver, thyroid tests, anti TTG – neg, PTH and 25 OH vitamin D - normal DXA: (same machine)

L2-L4 Total Hip Fem Neck Age 54 0.683 -3.6 0.737 -1.7 0.551 -2.7 Age 58 0.717 -3.3 0.754 -1.5 0.583 -2.4 % change + 4.9% * + 2.3% + 5.8% * 4 years ALN * Exceeds least significant change (technically responded)

?

Approved Therapies – PMO (10)

Spine Hip Non-vert ET/HT XX XX Calcitonin XX Raloxifene XX Alendronate XX XX XX Risedronate XX XX XX Ibandronate XX X Zoledronic acid XX XX XX Denosumab XX XX XX Teriparatide XX XX Abaloparatide XX XX

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Case 3 - Management

• Although compliant (ALN) + evidence of BMD

response  decision was to switch therapy IV zoledronic acid, denosumab, teriparatide

• Selected teriparatide (try different mechanism of

action – anabolic); alendronate and calcitonin D/C

• Reduced functional capacity - concern

– Seen regularly by Rehabilitation Med/Physical Therapy (inpt/outpt) – In hospital - seen by Spine Surgery/Ortho multiple times (vertebra-/kyphoplasty considered), pain improved, neg neuro exam; conservative/non-surgical course followed with bracing and spine protective measures – bending, lifting – Able to return to work eventually full-time

BMD Responses

L2-L4 Total Hip Fem Neck Age 54 0.683 -3.6 0.737 -1.7 0.551 -2.7

(Aln started, 3 yrs PM)

Age 58 0.717 -3.3 0.754 -1.5 0.583 -2.4

(painful L1 fracture; teriparatide started )

Age 59 0.755 -2.9 0.756 -1.5 0.560 -2.6 Age 60* 0.793 -2.6 0.761 -1.5 0.585 -2.4 % change +10.6% no no

(exceed LSC)

 *teriparatide d/c, denosumab started * Plan: 5 yrs denosumab (anticipate), follow w/zoledronic acid; now might consider initial combination (D-Mab + teriparatide; DATA study)

67 yo woman referred for 2nd opinion for severe osteoporosis in 2014

• Healthy except for hypothyroidism (x years), replaced

with T4, stable anemia, mild asthma

• Normal cycles, 2 pregnancies, menopause age 55
• No systemic steroids, use inhaled steroids for 3 yrs
• Dx with osteoporosis by DXA age 57; age 65 – radial

frx after tripping (ground level fall)

• Age 57-64: risedronate weekly (7 yr), then d/c
• Age 61-67 (when seen): raloxifene
• (Age 61-64: took both)
• Meds: never tolerated Ca suppl, ate high Ca diet (~5

servings dairy/d); vit D3 2000 IU/d; singulair 10 mg/d, raloxifene 60 mg/d; T4 0.100 mg/d

Case 4

• ROS: negative, +/- constipation
• FH: mother decreasing height, but no DXA done, no

frx (+breast cancer, MI)

• Habits: 7 pk-yrs smoking (d/c – 10 yrs previously), 7

glasses wine/week; 3-4 miles walking per day

• Exam: normal VS, 44.77 kg, 61 inches (154.2 cm);

mild pallor otherwise normal exam

Case 4

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L1-L4 Spine T score Fem Neck (left) T score

• 05/2014:

0.570 -4.3 0.510 -3.1

• 04/2012:

0.573 -4.3 0.540 -2.8

• 09/2010:

0.602 -4.0 0.511 -3.0

• 09/2007:

0.613 -3.9 0.515 -3.0

• 05/2006:

0.595 -4.1 0.509 -3.1

• 11/2004:

0.593 -4.1 0.514 -3.0 Total Hip (left) T score

• 05/2014:

0.554 -3.2

• 04/2012:

0.598 -2.8

• 09/2010:

0.621 -2.6

• 09/2007:

0.655 -2.4

• 05/2006:

0.624 -2.6

• 11/2004:

0.618 -2.7

Case 4 – Outside Hospital

No response to interventions

• LABS: CBC  Hgb/Hct 11.3 (mcv 85), BMP – nl

including Ca; nl LFTs, intact PTH; TSH 4.2, 25 OH vit D 43.7 ng/ml, SPEP- wnl

• 24 hr urine: Ca 84.6 mg (1968 ml, 742 mg creat)
• Bone turnover marker  serum C-telopeptide (lab
• btained C-peptide)
• Bone specific alkaline phosphatase - wnl

Case 4 - Evaluation

Refractory to oral bisphosphonate risedronate and raloxifene

• Options considered:

IV zoledronic acid, denosumab, teriparatide

• Secondary W/U continued 
• Hint: iron-def anemia (chart), low urinary Ca

Case 4 – Management

Refractory to oral bisphosphonate risedronate and raloxifene

• Options considered:

IV zoledronic acid, denosumab, teriparatide

• Secondary W/U continued 
• Hint: iron-def anemia (chart), low urinary Ca
• Anti-tissue transglutaminase AB: >1000 (nl <30);

ferritin 7 (10-291) iron 41 (29-189)

• EGD  complete villous atrophy (colo-neg)
• Instituted gluten-free diet and iron supplements 

U-Ca 135 mg, anemia/ferritin improved

Case 4 – Management

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L-Spine Total hip Fem Neck 2014

• 4.3
• 3.2
• 3.1 (outside)

11/2015 * 0.658 -3.5 0.636 -2.5 0.518 -3.0 12/2016 0.679 -3.3 0.633 -2.5 0.522 -3.0 2/2018 0.761 -2.6 0.685 -2.1 0.547 -2.7 % change + 15.6% + 7.7% + 5.6% *Started TPTD injections in 1/2015 ( 2/2017) 2/2017 - initiated Q 6 mo denosumab BMD response – reflects treatment x 3 yrs + gluten-free diet (can’t compare prior to current BMD – responded)

DXA Findings

1/2017

• Focused on younger women, treatment

naïve, treatment experienced

• Consider:

– All therapeutic options – Timing of medications, sequencing therapies, alternating mechanisms – Secondary etiologies – in patients not responding – repeat the workup

• Don’t be afraid to change therapies – if

things are not working

SUMMARY

Postmenopausal osteoporosis – evident at age 56

(+FH, smoking, petite body habitus, low Ca intake, +/-vit D)

• Complete workup: anti-tissue transglutaminase Ab

Management

• Optimize Ca and vit D3 intake (1200 mg, 2000 IU/d),

start wt bearing exercise (5/7 days per week), reduce lifting at work, STOP smoking

• FRAX - does not meet US thresholds  offer

pharmacologic therapy ?? (spine T score -3.1)

– Hormone therapy – Raloxifene – Bazedoxifene+CE (Duavee) – Bisphosphonate – Denosumab – Teriparatide

Approach to Management

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Postmenopausal osteoporosis – evident at age 56

• Complete workup: anti-tissue transglutaminase Ab,

spine films/CT (no occult frx) Management

• Optimize Ca and vit D3 intake (1200 mg, 2000 IU/d),

start wt bearing exercise (5/7 days per week), reduce lifting, STOP smoking

• FRAX - does not meet US thresholds  offer

pharmacologic therapy (spine T score -3.1)

– Hormone therapy * smoking concern – Raloxifene – Bazedoxifene+CEE (Duavee) * smoking concern – Bisphosphonate *** oral – no d/t GI bleed, ulcers – Denosumab – Teriparatide ** refused daily injections, missed 2 f/u appt’s – Abaloparatide (not available then)

Approach to Management