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4 types of antiresorptive medications

Antiresorptive medications slow the breakdown of bone

Bisphosphonates, RANKL inhibitors, SERMs, and estrogen are all types of anti-resorptive therapies

Antiresorptive medications table — drugs listed by type, benefits, side effects and issues, generic name (brand name), route of administration and dosing frequency

Drug type
(How it works)		 Benefits Issues
Side effects		 Generic name (brand name): ROA
Bisphosphonates

(inhibit mature osteoclasts, the cells that break down bone)
  • Reduce spine fractures by 40-70%
  • Reduce hip fractures by 30-50%
  • Well-studied with decades of safety data
  • Inexpensive (most are generic)
 Issue: Cannot be used in people with kidney disease

Side effects
Common:
Oral forms

  • Heartburn, stomach upset
  • Must be taken on empty stomach, sitting upright for 30-60 minutes

IV form

  • Possible flu-like symptoms after first dose (usually improves with later doses)

Rare and serious:

  • osteonecrosis of the jaw (1 year, 1 in 7,200)
  • atypical femur fractures 1 year, 1 in 56,200)
  • Alendronate (Fosamax®): weekly pill
  • Risedronate (Actonel®): weekly or monthly pill
  • Ibandronate (Boniva®): monthly pill or quarterly IV infusion
  • Zoledronic acid (Reclast®): yearly IV infusion

 
RANKL inhibitor

(inhibit the formation and function of osteoclasts, the cells that break down bone)
  • Very effective at reducing spine and hip fractures
  • No GI side effects
  • Can be used in people with kidney disease (unlike bisphosphonates)
 Issue: Cannot suddenly stop taking — stopping associated with risk of rapid bone loss and ‘rebound fractures’

  • Must transition to another anti-resorptive bone medication if discontinuing
 Denosumab (Prolia®): subcutaneous injection, once every 6 months at doctor’s office.
Selective Estrogen Receptor Modulator (SERM)

SERM = a drug that mimics or blocks estrogen depending on where it acts in the body

Acts like estrogen in bone → helps maintain bone density

 
  • Preserves or modestly increases bone mineral density Lowers the risk of vertebral fractures
  • Lowers total and LDL (“bad”) cholesterol without reducing HDL (“good”) cholesterol.
  • Reduces the risk of invasive breast cancer
 Side effects

Common

  • Hot flashes, especially in the first months of therapy
  • Leg cramps and muscle/joint pain
  • Swelling of hands, feet, or ankles
  • Flu‑like symptoms, fatigue, mild fever, or general body aches
  • Increased vaginal discharge or vaginal itching
  • Trouble sleeping, sweating

Serious/rare 

  • Increased risk of venous thromboembolism: deep vein thrombosis and pulmonary embolism
  • Possible increased risk of stroke in women with cardiovascular disease or high stroke risk factors
 Raloxifene (Evista®): Oral, as a tablet once daily
Estrogen
** only prevents bone loss while you take it
  • Prevents bone loss when started within 10 years of menopause.
  • Reduces fracture risk by approximately 30-40%
 Issue: Only protects bones while you’re taking it. When you stop, bone loss resumes at a rate similar to during menopause. All forms of systemic estrogen (pills, patches, gels) protect bones

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2 side effects of the bisphosphonates you might hear about

There are two rare, but scary side effects of the bisphosphonates class of medications used to treat osteoporosis. However, these side effects should be  considered in parallel with how well these medications work to prevent fractures that can come with series consequences and how infrequently they happen. In many cases these side effects happen when these drugs are used for cancer treatment at higher doses and for longer time frames than they are used in osteoporosis.

Osteonecrosis of the jaw (ONJ) is a condition where the jawbone is exposed and not covered by the gums. The bone weakens and dies.  The risk of ONJ is very low in people taking medications for osteoporosis, roughly 1/10,000 to 1/100,000.  However, the risk may be slightly higher with longer duration of bisphosphonate use (e.g. > 5 yrs) and in those who undergo invasive dental procedures, such as a tooth extraction or dental implant.  Good oral hygiene and regular dental care are the best ways to reduce the risk of ONJ.

Atypical femur fractures are a type of stress fracture originating in the lateral part of the thigh bone. They occur with minimal or no trauma and can occur in those who are taking antiresorptive osteoporosis medications, as well as in those who are not. One often feels pain in the thigh or groin area. The risk of suffering an atypical femur is very low, but increases with longer duration of use, such that the risk of AFF is <1 per 10,000 for less than 3 years of bisphosphonate use, rising to about 6 per 10,000 for 5 years or more of bisphosphonate use. This risk is higher in women of Asian descent.

Bisphosphonates prevent far more fractures than they cause atypical femur fracture — in White women, for every atypical femur fracture, bisphosphonates prevent roughly 75 hip fractures.

Duration Vertebral Fx Risk Reduction Hip / Nonvertebral Fx Risk Reduction ONJ Risk (≈ 1 in) AFF Risk (≈ 1 in)
1 year 60–65% (risedronate, zoledronic acid) Not established at 1 yr — trials underpowered for this endpoint 7,200 56,200
3 years 41–70% (varies by drug — see Table 1) Hip: 41–51%; Nonvertebral: 20–39% 1,460 7,960
10 years 55% (alendronate, continued vs. stopped at 5 yr) No direct 10-yr trial data point 300 270