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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 75 - Osteoporosis

Updated: Aug 3

“The most loving women are the women who will test you the most. She wants you to be your fullest, most magnificent self. She won’t settle for anything less. She knows it is true of you. She knows in your deepest heart you are free, you are Shiva. Anything less than that she will torment. And, as you know, she’s quite good at it.” - David Deida




PB#129 - Published September 2012 (Reaffirmed 2016)


Five Pearls

  1. In any hypoestrogenic state, resorption begins to overwhelm building, leading to decreased bone density.

  2. Treatment is warranted if T-score ≤ 2.5 on DXA scan or if patient has history of vertebral facture or other type of fragility fracture

  3. FRAX tool can be helpful in determining usefulness of treating patients in the osteopenic range (T-score < - 1 to ≥ -2.5). It predicts risk of osteoporotic fracture over next 10 years .

  4. Bisphosphonates are first-line therapy for all-comers, though raloxifene is also reasonable first-line in younger postmenopausal women.

  5. HRT is a great alternative to bisphosphonates in younger women at risk for osteoporotic fracture: ~35% decreased risk of hip fracture (estrogen alone or estrogen + progestin)


Background

- osteoporosis: any combination of loss of bone mass or change in bone architecture that carries increased risk of fracture

- bone mineral density (BMD) isn't the whole picture, as age and ethnicity are independent risks factor for fracture

- Caucasian women have higher risks of fracture than black women, while Latinos fall somewhere in between

- Chinese American women have lower average BMD but also lower risk of hip and forearm fracture than Caucasian women (perhaps architectural differences account for these associations)


Bone physiology

- bones are biodynamic

- 90% of an adult woman's bone mass is accumulated during childhood and adolescence

- bones develop to a large degree through heritable factors, but environmental factors are important in the expression of related genes

- bone remodeling is ongoing through adulthood: osteoclasts resorb bone, osteoblasts build bone (both cells are under the influence of the endocrine system and sex steroids)

- any conditions with associated estrogen deficiency leads to decreased BMD: anorexia nervosa, lactation, menopause, and prolonged use of depot medroxyprogesterone, GnRH analogues, or aromatase inhibitors

- in any hypoestrogenic state, resorption begins to overwhelm building, leading to decreased bone density; increased radical oxygen species are also attributed with bone loss seen with aging

- exercise early in life is associated with greater bone strength throughout life

- later in life, weight-bearing resistance exercise has been found to be most effective at maintaining strength of spinal vertebrae and walking is best for improving strength of hip bones

- vitamin D and calcium deficiency lead to Rickets in children and osteomalacia in adults (untreated --> osteopenia/osteoporosis)


Diagnosis

- dual-energy x-ray absorptiometry (DXA) of the hip and spine is the common method (and only test that has been validated)

Ten-year probability of sustaining any osteopathic fracture in women by age and T-score

- DXA scan results in a T-score that is a value that compares BMD to a young, healthy cohort of females (see Table 1)

- Z-score is also found in the report, which compares BMD to a cohort of women of similar age

- a female also has osteoporosis if they withstand a non-trauma-related fracture in an unexpected situation (e.g. vertebral fracture while opening a window or a simple fall from standing position)

- bone turnover markers (e.g. deoxypyridinoline and telopeptides) aren't helpful as they change on day-to-day basis


FRAX tool

- the fracture risk assessment tool (FRAX) was developed to predict the risk of osteoporotic fracture for a person over the next 10 years

- takes into account a number of factors: age, sex, BMI, parenteral hip fracture, smoking status, steroid use (≥5mg of prednisone daily for 3 months), alcohol intake ≥3 drinks daily, rheumatoid arthritis, and other secondary causes of osteoporosis

- can be helpful in determining usefulness of treating patients in the osteopenic range (T-score < - 1 to ≥ -2.5)

- only valid for women ≥40 years of age

- only recommended for women who are postmenopausal, not on osteoporosis treatment, and no prior hip or vertebral fracture


Who to treat?

- T-score ≤ -2.5 or if patient has history of vertebral facture or other type of fragility fracture

- FRAX report suggesting ≥3% risk of hip fracture or ≥20% risk of major osteoporotic fracture (forearm, hip, shoulder, or spine) if T-score < - 1 to ≥ -2.5 (osteopenic range)

- before treatment, consider secondary causes that might be reversible

Secondary causes of osteoporosis

- see Table 2

- start with a CBC, CMP, 24-hr urinary calcium level, 25-hydroxy vitamin D level, TSH

- follow-up studies: celiac panel, serum protein electrophoresis

- secondary causes may be involved if your patient seems to young to have a non-traumatic fracture or if Z-score is sufficiently low

Treatment options

- Bisphosphonates are first-line therapy for all-comers, though raloxifene is also reasonable first-line in younger postmenopausal women.


Bisphosphonates

- antiresorptive through osteoclast inhibition

- adverse effects: muscle pain, GI irritation, esophageal irritation, osteonecrosis of the jaw (rare: generally only seen with high IV dosing), seizures, and atypical femoral fractures

- keep patient sitting upright for ~30 min after taking it PO to minimize risk to esophagus (delayed-release formulations have lower risk)

- rather dramatic change in BMD may be seen 2-5 years after discontinuation, but given their long half-life, temporary discontinuation (e.g. dental procedures) is safe with no adverse effects

- zoledronic acid is GREAT because it's administered as an annual infusion, but it's contraindicated in renal failure


Estrogen agonist/antagonists

- aka selective estrogen receptor modulators

- antiresorptive through osteoclast inhibition

- Raloxifene is the only agent approved in the U.S. for this purpose (Tamoxifen has shown some benefit but not yet approved)

- pros: decreased vertebral fracture risk, reduced risk of breast cancer

- cons: no impact on hip fracture risk, increased risk of VTE, increased risk of death from stroke


Calcitonin

- antiresorptive through osteoclast inhibition

- available as nasal spray or IM injection

- shown to reduce vertebral fracture and to reduce pain related to vertebral fracture

- only works in women who are at least 5 years into postmenopausal state


RANK ligand inhibitors

- monoclonal antibody that inhibits osteoclasts by blocking RANKL (see image)

- Denosumab is only approved agent

- reduced risk of vertebral and hip fractures by 70% and 40%, respectively

- dosed q6 months


Source: Orthobullets.com


Parathyroid hormone

- two agents, but only parathyroid 1-34 (teraparatide) is approved in the U.S.

- works by improving bone architecture

- bone mineral content is lost quickly after discontinuation; add an anti-resorptive agent after discontinuation

- decreased vertebral and non-vertebral fracture risk

- not recommended for use >2 years as long-term use is associated with osteosarcoma


Hormonal therapy

- great alternative to bisphosphonates for younger women at risk for fracture (remember that the former comes with a bunch of side effects)

- approved for prevention of osteoporotic fracture

- higher doses are generally considered better for preventing fracture than the lower dose HRT that is more common today

- ~35% decreased risk of hip fracture (estrogen alone or estrogen + progestin)

- "safe" duration of therapy is unclear, though it's generally accepted that any increased risk of breast cancer from combined HRT doesn't happen until 3-5 years of treatment (probably much longer with estrogen therapy alone)

- when you discontinue HRT, best to start another agent like bisphosphonate within 1-2 years





How much Vitamin D and calcium should I recommend to my patients?

- 1000 - 1300 mg calcium (depending on age)

- 600 - 800 units Vitamin D (depending on age)

- see Table 4 for specs

- routine serum screening for vitamin D deficiency is not recommended

- data is all over the place with regards to the pros/cons of various serum Vitamin D levels (appears to follow a U-shaped curved --> too much or too little can be problematic)

- recommended upper limit of daily vitamin D intake is ~4000 units

- calcium supplementation may also be associated with cardiovascular risks, but jury is still out



Credit: Abu-Naser et al 2017

Do soy isoflavones have any effect on fracture risk?

- No.


Universal DXA screening begins at age 65

- there are specific situations (see Box 2) in which DXA screening may be appropriate before age 65

- FRAX can also be used to identify those patients in whom DXA screening before age 65 may be appropriate

- if 10-year major fracture risk is 9% or greater, this is the the equivalent fracture risk of the average 65-year old who has no additional risk factors --> screen!

- universal screening at time of menopause is not reasonable (without additional risk factors)

- repeat DXA in 15 years if T-score ≥ -1.5; in 5 years if -1.5 to -1.99; or annually if -2.0 to -2.49

- FRAX can be repeated annually to predict fracture risk --> DXA can then be done if necessary


Note: DMPA use is not an indication for DXA screening in the absence of other risk factors; remineralization of bone after discontinuation is rapid


How frequently should screening repeated after initiation of treatment?

- repeat DXA after initiating therapy --> remember that it takes 18-24 months to see a difference

- if on repeat DXA BMD is improved or stable, further screening is not recommended unless additional risk factors pop up



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