Chapter 49. Osteoporosis, Menopause, & Testosterone Use

Who is osteoporosis most commonly found in (low BMD)?

post-menopausal females

Vertebral fractures that occur without a fall might be hinted to by what symptom?

gradual decrease in height

What type of fracture is an early indicator in younger people?

Wrist fracture

Patient Characteristics Contributing to Osteoporosis Risk

• Advanced age

• Family hx

• Ethinicity (Increasd risk in caucasian and asian)

• Sex (females>males)

• Low body weight

Medical Diseases/Conditions Contributing to Osteoporosis Risk

• Diabetes

• Eating disorders

• GI disease

• Hyperthyroidism

• Hypogonadism in men

• Menopause

• RA/other autoimmune conditions

• Others: HIV/AIDS, epilepsy, Parkinson's

Lifestyle Factors Contributing to Osteoporosis Risk

• Smoking

• Excessive alcohol intake (≥3 drinks per day)

• Low calcium/vit d intake

• Physical inactivity

Medications contributing to Osteoporosis

• ASMs (carbamazepine, phenytoin)

• Aromatase inhibitors

• Depo-medroxyprogesterone

• GnRH agonists

• Lithium

• PPIs (inc pH dec's Ca absorption)

• Steroids (long-term use ≥ 5mg/day of prednisone or equivalent for 3+ months)

• Thyroid hormone (in excess)

• Others (loops, SSRIs, TZDs, tenofovir)

What is the gold standard to measure BMD and diagnose osteoporosis?

DEXA/DXA scan -> calculates a T or Z score

Who should have BMD measured?

All women 65+ and all men 70+

What score by the WHO estimates risk of fracture in the next 10 years?

FRAX tool

Interpreting a T-score?

• Negative score: at or above -1 correlates with stronger bones

• Normal = ≥ -1

• Osteopenia = -1 to -2.4

• Osteoporosis = ≤ -2.5

What is one of the most important lifetyle measures for patients with low BMD?

weight-bearing and muscle-strengthening exercise

What is required for calcium absorption?

Vitamin D - 1000 to 2000 IU daily

What diseases does Vitamin D deficiency cause?

children = rickets

adults = osteomalacia

Calcium absorption is ___________, so doses above ____________ should be divided.

saturable; 500-600mg

Calcium formulations

Calcium carbonate (e.g. Tums)

• 40% elemental calcium

• Absorption: acid-dependent (no PPIs)

• Must take w/ meals

Calcium citrate (e.g. Cal-citrate)

• 21% elemental calcium

• Absorption: NOT acid-dependent

• can take with or without food

Vitamin D Deficiency Management

• Required for Ca absorption

• Deficiency = serum vitamin D <30 ng/mL

• Treat with cholecalciferol (D3) or Ergocalciferol (D2)

- chole = 125-175 mcg daily

- Ergo = 1250 mcg weekly

Calcium Carbonate + Cholecalciferol

Caltrate

Elemental Calcium Equivalents

• 1g Calcium Carbonate = 400mg elemental Ca (40%)

• 1g Calcium Citrate = 210mg elemental Ca (21%)

Main side effect of calcium supplementation?

Constipation

Prevention vs Treatment therapies for Osteoporosis

Prevention

• Bisphosphonates (except IV ibandronate)

• estrogen-based therapies

• Raloxifene

Treatment

• Bisphosphonates

• Denosumab

• PTH hormone analogs (teriparatide)

• Calcitonin

Criteria for initiating treatment for decreased BMD

Osteoporosis

• T-score ≤ -2.5 (≤ -2 if diabetes) in spine, femoral neck, total hip or 1/3 radius OR

• Presence of a fragility fracture, regardless of BMD

Osteopenia (high risk)

• Low bone density (T-score btwn -1 and -2.5 AND

• FRAX score indicates 10yr major osteoporosis-related fracture of ≥20% or hip fracture probability of ≥3%

What is first-line for treatment OR prevention in dec. BMD patients?

Bisphosphonates

• PO admin = stay upright for 30 min (60 for ibandronate) and drink 6-8 oz water

• Side effects: esophagitis, hypocalcemia, GI effects

• RARE SEs: atypical femur x, Osteonecrosis of jaw (ONJ)

Treatment duration of Bisphosphonates

3-5 yrs in patients w/ low risk of fx (d/t risk of femur fractures and ONJ)

What drug is given SC every 6 months for decreased BMD and is an alternative to bisphosphonates?

Denosumab (Prolia)

• side effect = hypocalcemia

Which medication is for decreased BMD and is given SC but only for high-risk patients? (i.e. history of severe vertebral fractures)

Teriparatide (Forteo), Abaloparatide (Tymlos)

*PTH hormone analogs

Which drug used for bone diseases has a side effect of HYPERcalcemia?

PTH analogs (i.e. teriparatide)

What drugs are an alternative to bisphosphonates for dec. BMD if high risk of vertebral fx?

Raloxifene (Evista)

• Side effect: vasomotor sx

• increased risk for VTE and stroke

• Can be used in high breast cancer risk

conjugated estrogens/Bazedoxifene (Duavee)

• Also a tx for vasomotor sx

• Side effect: increased risk of breast, endometrial and ovarian cancer

• Used in women with intact uterus for osteoporosis prevention

Which drugs are last-line or not recommended?

• Estrogen (w/ or w/out progestin) for provention only in post meno women w vasomotor sx

• Calcitonin (Miacalcin) for tx only if other options not suitable (less effective; cancer risk w long term use)

Bisphosphonates MOA

Increase BMD by inhibiting osteoclast activity and bone resorption

All bisphosphonates reduce hip and vertebral fractures, except ___________, which only prevents vertebral fractures.

ibandronate

How long after using bisphosphonates should you initiate a drug holiday?

3-5 years of treatment

Other than decreased BMD, what are bisphosphonates indicated to treat?

hypercalcemia of malignancy (Zometa is zoledronic acid for this purpose - unlike Reclast for decreased BMD)

*Denosumab has indications for the same - Prolia for decreased BMD; Xgeva for hypercalemia of malignancy

Injectable and Oral bisphosphonates

Oral:

• Alendronate (Fosamax) -> tx dosing daily OR weekly

• Risedronate -> daily, weekly, or monthly dosing

• Ibandronate -> monthly

IV:

• Ibandronate -> q3 months

• Zoledronic acid (Reclast) -> once yearly

If esophagitis is present, what formulation should be used?

injectable bisphosphonates (d/t risk for esophageal cancer)

Side effects of bisphosphonates

PO/IV:

• Contraindicated in hypocalcemia

• Renal impairment warning

• ONJ

• Femur fractures

• esophagitis, esophageal ulcers, erosions (follow admin instructions with timing and water)

• Hypocalcemia must be corrected prior to use

• Dyspepsia/dysphagia/heartburn/NV (oral only)

counseling: dental work should be completed prior to starting tx d/t risk of ONJ; separate from Ca, antacids, iron, and Mag by at least 2 hours

What is the brand name for delayed release risedronate?

Atelvia -> do not use with H2RAs and PPIs; requires acidic gut

Raloxifene Boxed Warning

Increased risk of VTE; incrased risk of death d/t stroke

• Contraindicated in pregnancy and hx of VTE

• side effects: Hot flashes, peripheral edema, arthralgia, leg cramps

Boxed Warnings for Duavee

• Endometrial cancer (d/t unsuppressed estrogen)

*(also increases risk of breast and ovarian cancer but not a boxed warning)

• Increased risk of DVT and stroke

Contraindications: pregnancy and VTE (like raloxifene), as well as breast cancer hx and undiagnosed uterine bleeding

Which drug for decreased BMD is available as a nasal spray?

Calcitonin (also an injection)

*one nostril daily; alternate nostrils

Calcitonin (Miacalcin) warnings

• Hypocalcemia

• Increased malignancy

• Hypersensitivity to salmon-derived products

Calcitonin (Miacalcin) MOA

inhibits bone resorption by osteoclasts

PTH Hormone 1-34 MOA

analogs of PTH, increasing bone formation

(e.g. Teriparatide, abaloparatide)

teriparatide good for glucocorticoid-induced

How are PTH Hormone 1-34 administered?

• SC daily

• Refrigerate

• Forteo: Protect from light

PTH Hormone 1-34 Warnings/Side effects

• Osteosarcoma (bone cancer)

• Hypercalcemia

• Arthralgias

• Leg cramps

• Nausea

• Orthostasis/dizziness

Which drug is indicated for the treatment of osteoporosis when there is a high risk of fracture?

Denosumab (Prolia)

• Injected Q6Months

Boxed Warning for Denosumab

Hypocalcemia in patients with advanced kidney disease

• Contraindications: hypocalcemia; pregnancy

• Warnings: ONJ, femur fractures (same as bisphosphonates)

• Side effects: HTN, fatigue, edema, NVD, decreased PO4

Denosumab is a mAb that binds to what receptor to prevent osteoclast formation?

Denosumab

When is menopause said to have been reached?

Last menstrual period >12 months ago

What hormonal changes can result in vasomotor sx?

decreased estrogen and progesterone -> traditionally experienced in perimenopause

*hot flashes, night sweats, vaginal dryness, burning, dyspareunia (painful intercourse)

What is the most effective tx for vasomotor control?

Estrogen -> decrease in luteinizing hormone (LH) = more stable temperature control

What formulations of estrogen are associated with a lower risk of VTE and stroke than standard oral doses?

Transdermal, local (topical), and low-dose oral

*topicals bypass 1st pass metabolism; can use lower doses also d/t this

What formulation of estrogen is preferred for patients who have vaginal symptoms only?

Local estrogen

What medication should women with a uterus be given for menopausal hormone theray?

Combination estrogen and progestin

(unopposed estrogen = increased risk of endometrial cancer)

What treatment is most effective for menopausal women with vasomotor sx?

Estrogen

Which medication for menopause may cause mood disturbances?

progestin

Are micronized or synthetic progestins safer?

Micronized (e.g. Prometrium)

(synthetic = medroxyprogesterone)

What are the criteria for hormone therapy for menopause?

• Healthy, symptomatic women within 10 years of menopause, ≤60, and no contraindications to use

• If patient >60, may be acceptable (i.e. osteoporosis) with lowest dose and pt advised of safety risks

• Use non-hormonal tx for patients with risk factors

Local Hormone Therapies

17-Beta-Estradiol

• Estrace (cream)

• Estring (ring)

• Vagifem (vaginal tablet)

Conjugated Equine Estrogens

• Premarin (cream)

Systemic Hormone Therapies

Estradiol

• Climara (patch)

• Vivelle-Dot (patch)

17-Beta-Estradiol

Conjugated Equine Estrogens

• Premarin (oral tab, injection)

Conjugated Equine Estrogens + Medroxyprogesterone

Medroxyprogesterone

• Provera (oral tab)

Micronized progesterone

• Prometrium (oral tab)

Estradiol patch dosing

• Climara = once weekly

• Vivelle-Dot = twice weekly

Which medication is an oral estrogen agonist/antagonist indicated for dyspareunia?

Ospemifene

*only for moderate-severe sx, NOT MILD

Which SSRI is FDA approved for vasomotor symptoms?

Paroxetine (Brisdelle)

What medication that is important for women's health interacts with paroxetine?

Tamoxifen blocked effectiveness; Paroxetine is a CYP 2D6 inhibitor

Which drug is a neurokinin B antagonist for menopausal vasomotor sx?

Fezolinetant (modulate thermoregulatory center; vasomotor sx)

Which medications are NOT recommended for vasomotor sx d/t risk of adverse effects?

Clonidine, pregabalin

Natural products for vasomotor sx

• black cohosh

• evening primrose oil

• red clover

• soy

What are common examples of medications that decrease testosterone?

• Opioids (especially methadone)

• Chemotherapy for prostate cancer

• Cimetidine

• Spironolactone

What does testosterone use carry a risk of?

cardiovascular risks; increased clotting risk (increases hematocrit)

side effects: noncancerous prostate growth, male pattern baldness, acne, gynecomastia, increased appetite, edema, hepatotoxicity, reduced sperm count

*Testosterone and anabolic androgenic steroids carry a warning for abuse potential & serious adverse events

Who is testosterone indicated for?

restricted to men with severe BPH (prostate growth)

Formulations of testosterone

gel, IM or SC injections -> injections are painful

Testosterone gel brand

AndroGel, AndroGel Pump

Boxed Warning for Testosterone

Secondary exposure to testosterone in children can result in early virilizatiton

Testosterone name for injection

Testosterone cypionate

What side effect does Natesto carry?

nasal irritation (testosterone nasal gel)

Counseling for testosterone replacement products

Gels: apply at same time each morning

What DEA class are testosterone products?

C-III