Achy Breaky Bones

Hilary Rowe, BScPharm

VIHA Pharmacy Resident 2009-10

Geriatrics Rotation

Sept 30, 2009

Outline

• Objectives• Introduction to the Patient• Review of Systems• DRP’s• Osteoporosis• Evidence• Recommendation• Monitoring

Objectives

• Review pathophysiology & diagnostic criteria for osteoporosis

• Review Evidence of teriparatide & zoledronic acid

• Discuss therapeutic options for a 94 yo osteoporotic female

• Discuss decision & monitoring

Mrs. FT

• ID: 94 yo female• Admitted:

– urinary retention from a UTI (resolved)

• Allergies: – Sulpha (reaction unknown)

• SH:– Lives alone, medications in vials, Pharmanet

regular, no Hx smoking, alcohol 2 oz drink before dinner

Mrs. FT

• Discharge Plan: – Return home to independent living

• PMHx: – Oophorectomy, hysterectomy, fractures, HTN,

GERD • Meds PTA:

– Felodipine, Cilazapril, Rabeprazole, Calcitonin, Tramadol/Acetaminophen, Alendronate, Acetaminophen, Calcium, Vitamin D

Review of Systems

System Findings Medications

CNS •MMSE 25/28•Dizzy if moves to quickly•Sleeping pill effective but wants to discontinue

Taper Zopiclone 3.75mg prn

Psych •Complains of low mood Started Mirtazapine 7.5 mg

EENT •Bilateral Cataract Surgery•Hearing Aids

Review of Systems

System Findings Medications

Cardio •Hypertension x 10 years

BP Sept 20-22nd : 120/78, 110/75, 138/85 mm Hg•Mitral Incompetence

Felodipine 2.5mg daily

Cilazapril 5mg daily

GI/Liver •GERD•Bowel movements q 3 days

Lansoprazole 30mg daily

Fruitlax daily

Review of Systems

System Findings Medications

MSK •Fracture right hip healing (March 09)•Hx fracture right wrist•Compression fractures of the spine: recent Sept 18th bone scan T12 & T3, old T8, T9, T10, T11, T12, L1, L4

Calcium carbonate 500mg elemental BID

Vit D 1000 Units daily

Alendronate 70mg Q Thursday (Started Oct 08)

Calcitonin nasal spray (Started Aug 12, 09)

Review of Systems

System Findings Medications

Pain •Upon ER admission-pain when transferring at home currently using pain scale to assess efficacy of Tramdol/ Acetaminophen and pain with physio

Tramadol/ Acetaminophen QID (Started Aug 12)

Calcitonin nasal spray (Started Aug 12)

Hydromorphone 0.5mg q 2h prn

Renal/ GU

•Retention from UTI (resolved)

Review of SystemsSystem Findings Medications

Heme •Sept 18th RBC 3.37 (↓), Hgb 118 (↓), Hct 0.34 (↓), MCV 101 (↑), RCDW 14.7 (↑)

Fluids/ Lytes

•K+ Sept 22nd & 28th 4.1 mmol/L•SIADH

-Urine Osmolality Sept 22nd 582 mmol/kg, 23rd 417mmol/kg

-Urine Na 114mmol/L Sept 22nd

-Na 130 mmol/L (↓) Sept 18th Na 134mmol/L (↓) Sept 28th

K+ 600mg SR BID

Salt on food, no fluid restriction yet

DRP’s

• Mrs. T requires continued assessment of pain on transfer and with physio despite present therapy of tramadol/Acetaminophen, calcitonin, and prn hydromorphone

• Mrs. T is at risk of unsteadiness and falls secondary to low Na and would benefit from monitoring and continued re-assessment of her fluid and salt intake

DRP’s

• Mrs. T is at risk of falls secondary to experiencing a drug-drug interaction with mirtazapine and alcohol causing drowsiness and a hangover effect and would benefit from counseling in regards to alcohol intake

• Mrs. T continues to experience multiple painful fractures despite standard therapy of Alendronate, Ca and Vit D and may benefit from consideration of additional therapies.

Osteoporosis

• Osteoclasts - ion channels that pump protons into extracellular space, ↓ in pH dissolves bone

• Osteoblasts deposit new bone

• Balance between these cells determines if bone is made, maintained, or lost

Osteoporosis

• Low bone mass and fragility due to:– peak bone mass is low– bone resorption is excessive

• trabecular bone loss and increased porosity in compact bone

– bone formation during remodeling is decreased

• Diagnosed by fragility fracture or T score <-2.5

Mrs. FT

• Patient is on Calcium, Vit D, Calcitonin, Alendronate

• Fracture right hip healing (March 09)• Compression Fractures of the spine: recent

Sept 18th bone scan T12 & T3• Lives alone• Cognitively intact and no compliance issues

Goals of Therapy

• Reduce hip and vertebral fractures • Prevent hospitalizations• Control Pain• Reduce side effects• Keep patient living independently (quality of

life)• Limit financial burden

Therapeutic Options

• Alendronate 70mg weekly

• Zoledronic acid 5mg infusion yearly

• Teriparatide 20 mcg subcutaneous injection daily

Studies to Discuss

• Alendronate vs Teriparatide– Alendronate: Decreases the rate of bone

resorption by blocking osteoclasts

• Zoledronic acid vs Placebo– Zoledronic Acid: Inhibits osteoclast resorption,

reducing bone turnover

• Teriparatide vs Placebo– Forteo: acts on osteoblasts to stimulate new bone

growth and improve bone density

Body et al. J Clin Endocrinol Metab 2002

P •Women 5 years post menopause 30-85 yo

I •Teriparatide 40mcg inj daily + po placebo

C •Placebo inj + Alendronate 10mg daily

O Results: 1º-Lumbar Spine (LS) DXA

Alendronate ↑6.6% (P<0.001), Teriparatide ↑ 15.1% (P<0.001)

2º-New Non vertebral fracture NNT 10 (P 0.042)

–AE:Mild hypercalcemia, leg cramps

S •Multicenter trial x 24 mo (ended at 14 mo)

Black et al. New Engl J Med 2007

P •Post menopause women 65-89 yo, •Previous bisphosphonate use = 2 yr wash out•Stratum 1-no Rx at time of randomization •Stratum 2-allowed Rx (raloxifene, calcitonin, medroxyprogesterone etc.)

I •Zoledronic acid 5mg IV infusion over 15 min

C •Placebo IV infusion over 15 min

Black et al. New Engl J Med 2007

O Results:

1º- New vertebral fracture (Stratum1) NNT 18

- New Hip Fracture NNT 107

2º- Any non vertebral fracture NNT 40

- Any clinical fracture NNT 26

- Clinical vertebral fracture NNT 60

- >2 vertebral fractures (Stratum 1) NNT 66

-↑ in BMD of total hip 6.02%, LS 6.71%, femoral neck 5.06% (P<0.001)

S •Multicenter trial x 24 mo (ended at 14 mo)

Neer et al. New Engl J Med 2001

P •Women previous vertebral fractures, ambulatory, 5+ years post menopause, average age was 69 years old

I •Teriparatide 20mcg subcutaneous daily

C •Placebo subcutaneous daily

O •Decrease in hip and vertebral fractures

S •Multicenter placebo controlled trial, over 24 months (average follow up 21 months)

Neer et al. New Engl J Med 2001

Outcome RR RRR ARR NNT/NNH

>1 New Vertebral Fracture

0.35 0.65 0.09 10.7

>1 New Fragility Fracture

0.47 0.53 0.03 34

Dizziness 0.03 0.7 0.03 34

Leg cramps 0.03 0.7 0.02 50

↑ BMD LS 9%, 3% femoral neck, total BMD 2%**Maximum exposure: Not >18 months, showed osteosarcomas in rats

Patient Considerations

• Cost $15,000 per 18 months

• Need to apply to Forteo Customer Care• Can patient do injections?• Can patient remember daily regimen?• Benefit to patient?• Drug interactions?

Recommendation

• Teriparatide 20mcg subcutaneous daily for 18 mo

• Have Forteo nurse teach patient in hospital• Calcium carbonate 500mg elemental BID• Vitamin D 2000 units daily• Continue to mobilize with walker

                                                  

Monitoring

Adverse Effects

Monitor When Who

Dizzy/Lightheaded After daily inj Patient & Nurse

Leg cramps After daily inj Patient & Nurse

Serum Calcium Baseline, q6mo Physician

Urine Calcium Baseline, q6mo Physician

Uric Acid Baseline, q6mo Physician

Renal Function Baseline, q6mo Physician

Monitoring

Efficacy

Monitor When Who

New Fractures Ongoing Patient/Physician

Vit D & Calcium intake

At refills Pharmacist

Compliance- patient injecting daily & rotating sites

At refills Pharmacist

References

• Neer RM, Arnaud CD, Zanchetta JR et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. New Engl J Med 2001;344:1434-41.

• Black et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New Engl J Med 2007;356:1809-22.

• Body JJ, Gaich GA, Scheele WH et al. A randomized double-blind trial to compare the efficacy of teriparatide [Recombinant Human Parathyroid Hormone (1–34)] with alendronate in postmenopausal women with osteoporosis. The Journal of Clinical Endocrinology and Metabolism 2002; 87(10):4528–4535.

Questions?