Osteoporosis - Lewis

What are the risk factors that increase risk of osteoporosis?

1. Low BMD

2. Age (≥65 years for women)

3. Female sex

4. Race/ethnicity

5. Low BMI

6. Smoking

7. Menopause

8. +3 drinks/day

9. Genetics

10. Inadequate nutrition/exercise

11. Weight bearing exercise

12. History of fracture

13. Falls

What medications are risk factors of osteoporosis?

1. Anti-epileptics

2. Medications that lower estrogen (aromatase inhibitors)

3. Chemotherapy

4. Medroxyprogesterone

5. PPIs

6. Glucocorticoids

7. SSRIs

8. SGLT2i

9. TZD (pioglitazone)

10. T4

11. Diuretics

What lab values do you look at to test for osteoporosis?

1. CMP

2. 25(OH) vitamin D (low)

3. TSH (low)

4. Total testosterone (men)

5. 24 hour urine calcium and creatinine concentrations

6. CBC

Evaluate patients’ need for bone-remodeling medication treatment

1. Women aged ≥65 years

2. Postmenopausal women aged <65 with ≥1 clinical risk factor

• Should get a central DXA when the FRAX major osteoporotic fracture risk score is >8.4%

3. Men aged ≥50 years with ≥1 clinical risk factor

4. If no secondary cause of osteoporosis or history of a low-trauma fracture, BMD screening not recommended for children, premenopause, males younger than 50

What does a DEXA scan do?

Assesses bone mineral density

What is a T-score?

Number of SD from the mean of the reference population

What DEXA score is used for diagnosis of osteoporosis?

T-score ≤ -2.5

What does the T-score compare the patient’s BMD to?

A healthy young white female

What does the Z-score compare the patient’s BMD to?

The BMD of someone of the same age and gender

How often should you do routine checkups (DEXA) for BMD?

• Every 1-3 years if treated for osteoporosis

• Every 2-5 years at low risk of fracture and not receiving treatment

What do the different T-score values indicate?

How do you diagnose osteoporosis in postmenopausal women?

What are the goals of treatment for osteoporosis?

• Not curable

• Strengthen bones and reduce fracture risk

• Minimize bone loss

• Reduce fall risk

• Pain management

What are some lifestyle modifications to prevent osteoporosis?

• Adequate intake of calcium and vitamin D

• Diet

• Weight-bearing/resistance exercises

• Smoking cessation

• Avoid heavy drinking

• Reduce fall risks (BEERs meds)

What are the recommended calcium daily intakes for men?

• 19-70 years old: 1000 mg calcium/day

• >70 years old: 1200 mg calcium/day

What are the recommended calcium daily intakes for women?

• 19-50 years old: 1000 mg calcium/day

• >50 years old: 1200 mg calcium/day

What are the ADRs associated with calcium?

• Dyspepsia

• Constipation

• Kidney stones

What should you separate calcium from?

Thyroid hormones and irons

Which calcium supplements are most widely used? What are the pros and cons?

• Calcium carbonate (first choice)

  • Cheapest

  • Must take with meals

  • Not recommended in patients taking PPIs/H2RAs

• Calcium citrate:

  • More expensive

  • Can be taken with or without meals

  • Good for patients on PPIs/H2RAs

What is the difference between Ergocalciferol (D2) and Cholecalciferol (D3)?

• D3 is preferred because it increases serum 25(OH)D more efficiently than D2

• D2 does not accurately measure all vitamin D assays

• Both can be taken with or without food

Who should be given vitamin D supplementation?

Adults with osteoporosis or at high risk of it

What are the suggested vitamin D intakes?

• AACE: 1000-2000 IU daily

• NOF: 800-1000 IU daily

• IM: 600 IU daily

When do you give pharmacological treatment assuming postmenopausal females and males 50+ years old?

• T-score ≤ -2.5 at lumbar spine, femoral neck, total hip

• History of fragility fracture of vertebrae (clinical or subclinical), hip, wrist, pelvis, humerus

• T-score between -1 and -2.5 at femoral neck or spine AND

  • 10-year probability of hip fracture ≥ 3% OR

  • 10-year probability of major osteporosis related fracture ≥ 20%

What are the FDA approved medications for prevention of osteoporosis on postmenopausal women?

• Estrogens

• Bisphosphonates: alendronate, risedronate, ibandronate, zoledronic acid

• SERMs: raloxifene, bazedoxifene

• none for men

What are pharmacological treatment options for patients with high risk but no prior fractures?

• Alendronate, denosumab, risedronate, zoledronic acid

  • Can try ibandronate and raloxifene

• If BMD worsens, switch to injectable or anabolic agent

What are pharmacological treatment options for patients with very high risk and prior fractures?

• PTH analogs, romosozumab, zoledronic acid

• Can also try alendronate, risedronate

What drugs are most commonly used in osteoporosis?

Bisphosphonates

Which bisphosphonate is given IV only?

Zoledronic acid (Reclast)

Which bisphosphonate can be given PO or IV?

Ibandronate (Boniva)

Which bisphosphonate is only for osteoporosis in postmenopausal women?

Ibandronate (Boniva)

What do you have to consider when initiating bisphosphonates?

• Do not use alendronate or zoledronic acid if CrCl <35 mL/min

• Do not use risedronate or ibandronate if CrCl <30 mL/min

What types of osteoporosis can bisphonates be used for?

Alendronate, risedronate, zoledronic acid: treatment and prevention of postmenopausal osteoporosis, treatment to increase bone mass in men with osteoporosis, glucocorticoids-induced osteoporosis

Ibandronate: treatment and prevention of postmenopausal osteoporosis ONLY

How should you counsel patients on taking bisphosphonates?

• Take on empty stomach with 6-8 ounces of water

• Do not lie down, eat/drink for at least 30 minutes (60 minutes for ibandronate)

What are the side effects associated with bisphosphonates?

• Common: abdominal pain, dyspepsia, hypocalcemia

• Rare: osteonecrosis of the jaw (ONJ), ulcers, bone pain, atypical fractures

  • Recommend routine dental exams

  • Dental procedures should be done before therapy

What is ONJ?

• Overgrowth of bone in the jaw

• Seen in high doses of IV bisphosphonates

What is an atypical femoral fracture?

• Seen in long term bisphosphonate use but not exclusive to bisphosphonates

• May be caused by slow bone turnover

Why should patients go on a bisphosphonate drug holiday?

• Bisphosphonates tend to reside in the bones for continued efficacy after discontinuation

• Going on holiday decreases risk of side effects like ONJ and atypical fractures

How long should bisphosphonates be used for?

• 5-10 years

• 3-6 years for zoledronic acid

What medications can you initiate during a bisphosphonate holiday?

Teriparatide or raloxifene

What medications can you initiate for other drug holidays?

• Anabolic agents: denosumab, bisphosphonates, raloxifene

• Denosumab: antiresorptive agents (don’t use anabolic agents)

How is denosumab (Prolia) administered?

60 mg SC every 6 months

What is the BBW for denosumab?

Severe hypocalcemia in patients with advanced kidney disease

What are the side effects associated with denosumab?

• Hypocalcemia

• Injection site reaction

• ONJ

• atypical fractures

• Infection

What should you do after discontinuing denosumab?

Initiate another antiresportive agent since the BMD will decline

What medication is only indicated for treatment ONLY for postmenopausal women, typically for patients who have failed bisphosphonates and denosumab?

Calcitonin (Miacalcin, Fortical)

How is calcitonin administered?

• Intranasal: 1 spray into one nostril only

• SC

What are the side effects of calcitonin?

• Rhinitis (if intranasal)

• Hypocalcemia

• potentially increased risk of malignancy

Which medication should not be used if the patient has a salmon allergy?

Calcitonin

What treatment is used in prevention of osteoporosis in postmenopausal women but is not FDA indicated?

Estrogen

If a patient does not have a hysterectomy, what do you have to add to estrogen regimens? Why?

• Progesterone

• Estrogen alone causes uterine cancer

What is the BBW of estrogens?

Do not use for prevention of CVD or prevention of dementia, increases risk of breast cancer

What are the common side effects of estrogen?

Headaches, weight gain

What is bazedoxifene/estrogen (Duavee) used for?

Prevention of osteoporosis in postmenopausal women

When would bazedoxifene/estrogen (Duavee) be contraindicated?

History of/current VTE, pregnancy, carcinoma of the breast

What is the BBW of bazedoxifene/estrogen (Duavee)?

• Increased risk of stroke/DVT

• Do not use to reduce risk of CVD/dementia

• Do not take with other estrogen products

• Increases risk of endometrial cancer in patients with a uterus who use unopposed estrogens (basically means estrogen without progesterone)

What are the common side effects of bazedoxifene/estrogen (Duavee)?

Nausea, dizziness, muscle spasm, leg cramps

When is raloxifene (Evista) contraindicated?

History of/current VTE, pregnancy

Why is raloxifene better than estrogen based products?

Is a mixed estrogen agonist/antagonist so prevents bone loss and decreases risk of breast cancer in postmenopausal women

What is the BBW for raloxifene (Evista)?

Increased risk of DVT/PE/stroke

What are common side effects of raloxifene (Evista)?

Hot flashes, peripheral edema, leg cramps, muscle spasms

What are PTH analogs indicated for?

Osteoporosis treatment

How do you store PTH analogs?

• Teriparatide: refrigerate

• Abaloparatide: refrigerate, but can store at RT for 30 days once opened

How are PTH analogs administered and for how long?

SC and up to 2 years

What is the BBW for PTH analogs?

Potential risk of osteosarcoma (malignant bone tumor)

What are common side effects of PTH analogs?

Rapid bone loss after discontinuation, transient hypercalcemia, orthostatic hypotension, nausea

What is romosozumab (Evenity) indicated for?

Osteoporosis in post-menpausal women

How is romosozumab (Evenity) administered and for how long?

• Two consecutive injections monthly

• Used up to 1 year

What is the BBW for romosozumab (Evenity)?

• Increased risk of MI, stroke, cardiovascular disease

• Do not initiate in patients with MI/stroke within a year

What are the side effects of romosozumab (Evenity)?

Arthralgia, headache, hypersensitivity, injection site reactions

What do you monitor for in any osteoporosis treatment?

• Monitor BMD every 1-3 years while on treatment

• Goal: increased/stable BMD