Bone Fragility

Bone Fragility Treatment

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Since we first started using bisphosphonates like alendronate (Fosamax) to treat bone loss in women, our tendency has been to over treat younger women with milder bone loss and under treat older women who are at much higher risk of fracture, or in some cases recurrent fracture.

All too often, I see postmenopausal women in my practice who have had a hip fracture, or a fracture at another site, yet are not on any medication to strengthen their bones. Many have not even had a DXA (bone density test). Most have not had a vitamin D level checked. This is not because they are neglected, but because there is uncertainty about who is responsible for the testing and treatment of these patients, and there is also fear of side effects of medications, especially bisphosphonates.

I hope to clear up some of this confusion. I think that any physician or provider with a good understanding of the problem of bone fragility and possible solutions can potentially help a lot of patients avoid fractures.

  1. Identify patients at risk of fragility fractures.
    If a patient has had a recent (last 5 years) fracture as a result of a fall from standing height, he or she is at high risk of another fracture. A DXA (dual-photon bone density of hips, spine, or wrist) should be done. Women should be tested (DXA) when they are postmenopausal, and when they stop taking HRT or ERT. Men should be tested by age 70, sooner (55) if they have risk factors. Significant risk factors other than personal history of fracture include smoking cigarettes, use of steroids, family history of osteoporosis or hip fracture, and height loss or kyphosis. The older the patient is, the higher the risk of fracture.
  2. Replace vitamin D
    Half of the patients who have bone loss are vitamin D deficient. Serum 25-hydroxy vitamin D should be 30ng/ml or more to keep PTH levels suppressed. Replace vitamin D by giving 50,000 units of D2 or D3 weekly for 8-12 weeks, then 1000-2000 units daily with calcium. Wait 6 or more weeks after the last 50k dose before rechecking levels. Toxicity is extremely rare (only at levels above 150 ng/ml), this is not like vitamin A.
  3. Recommend calcium
    Postmenopausal patients should receive 1000 mg to 1200 mg calcium daily, I try to get them to take at least one dose daily. For patients with GI problems: slow release or chewable calcium.
  4. Osteopenic: FRAX calculation
    If a patient’s T scores are between -1 and -2.5, use the FRAX tool (http://www.shef.ac.uk/FRAX/) to calculate 10-year fracture risk. Treatment levels are >20% risk of any fracture or >3% risk of a hip fracture. If the risk level is below that, check vitamin D and give calcium, etc., but not drug therapy! You can do the FRAX calculation without a bone density, just basing it on age and other factors, though it is not as accurate or predictive. Just enter the other data that you do have, such as age, weight, smoking, family history, etc.
  5. Treat osteoporosis in postmenopausal women
    You don’t need a FRAX analysis on this group, nor do you have to worry that you may be missing some secondary cause of bone loss! If the T score is less than -2.5 then treatment is indicated. By definition, a fragility fracture in a postmenopausal patient would make the diagnosis of osteoporosis too, but a DXA should be obtained before treatment so that the patient can be followed.
  6. Treatment: consider parenteral therapy
    Especially for a patient with a prior fracture, relying on oral agents is probably not the best plan. Patients have a hard time being compliant. IV Reclast or SQ Prolia are good, effective choices that do not rely on oral absorption. Most patients accept these drugs readily and side effects are minimal. Insurance or Medicare coverage is good, so cost with parenteral therapy is often less than with oral.
  7. Follow DXA every 2 years
    The main reason is to make sure the patient is not continuing to lose bone. This could happen if the patient is noncompliant on oral therapy (not a problem if Reclast or Prolia were used), or if there is a rare secondary cause of bone loss. It is very helpful and reassuring to the patient to see a gain in bone density with treatment, even if it is small.

I think that many physicians and providers are hesitant to give bisphosphonates because of the perceived risk of ONJ (Osteonecrosis of the jaw) and atypical fractures. The risk of an atypical fracture due to the use of bisphosphonate is about 5 per 10,000 patient-years of treatment. The way to get around this is to offer a drug holiday (see below). Every year off the drug decreases the risk of an atypical fracture by 70%. ONJ occurs at a rate of 0.10% of patients treated, but definitions of what ONJ is differ.

After at least 3 years on bisphosphonate therapy, a “drug holiday” may be appropriate. There is good evidence that even if medication is stopped, bone density is stable for up to 5 years. Fracture rates do not go up for several years after therapy is stopped, mainly because the drug actually binds to bone, so it can remain active.

In the case of younger, premenopausal patients, or in men, the strategy is a little different. I would probably hold off doing a DEXA until menopause, or age 50 in men. Patients with 2 or more risk factors should have a DEXA early, patients with no risk factors could perhaps wait until age 65; however, risk factors do not predict bone density. Risk factors include:

  • Personal history of fracture (excluding fingers, hand, toes, foot or skull)
  • Smoking
  • Family history of fracture, especially if mother fractured her hip
  • Use of steroids, oral or inhaled, on a daily basis
  • Height loss of over 1 inch or dowager’s hump (kyphosis)

If you get a DEXA in a younger person, the T score is not very helpful; the Z score is a more useful value. In a younger patient there is less overall concern about fracture risk, and more concern about absolute bone density, that may help to predict fracture risk in the future. A Z score compares the patient to a patient of “average” bone density, of the same age. This does not predict fracture risk like a T score does, which compares all patients to a standardized value of peak bone mass.

If the Z score is -2 or less, the patient is said to have “low bone mass” (density) and possible causes should be explored. Besides the risk factors above, there are some other reasons for bone density to be abnormally low:

  • Malabsorption (from GI disease like sprue or Crohn’s disease)
  • Patients who had gastric bypass, for obesity
  • Low vitamin D
  • Hyperparathyroidism, either primary or secondary
  • Renal disease

In the case of a patient under age 50, less emphasis should be on treatment and more on diagnosis of a cause of bone loss. If the cause can be found and dealt with, that would be a better choice than using a drug like a bisphosphonate. In a patient under 50 with “low bone mass” and a fracture, I would consider the use of Forteo (teriperatide). This is a drug given by daily injection, thru a small needle like insulin, which can rebuild lost bone quickly and effectively. The drug is typically given for 2 years and then stopped.

Men over 50 should be treated in the same way as postmenopausal patients. The one other consideration here would be to check a morning serum total testosterone level, which should normally be over 300 ng/dL. Lower levels may be associated with symptoms such as low libido and reduced strength and muscle mass, and could be treated by testosterone replacement therapy. This would also improve bone mass.

More awareness and attention to this problem would lead to earlier diagnosis and treatment, and prevent more fractures. With proper workup and treatment, the rate of hip fracture could be reduced by 40% or more. We should not be reluctant to order DEXA testing and treat the patient appropriately. ONJ and atypical fractures added together are a much, much smaller problem than hip and spine fractures.

 

Last week, you gave your answers. This week, we give ours.

  • Would you order a DEXA in a 30-year-old white female who smokes and is on Depo Provera?
    Answer: No. In general, these aren’t factors in increasing bone fragility, though they may decrease bone density. Depo Provera may decrease density by 6% but no increase in fracture risk has been shown. It would be good to advise such a patient to not smoke and take calcium but I would not order a DEXA.
  • Does it matter which oral bisphosphonate we use? I.e., is Boniva equal to Actonel and Fosamax?
    Answer: There are differences but they are subtle. They all increase bone density to about the same degree but Actonel (risedronate) has better data as far as fracture reduction at hip, spine, and nonvertebral sites. Dosing and cost are considerations too, with Fosamax (alendronate) being generally cheaper and Boniva (ibandronate) and Actonel being monthly dosing. If the patient does well with a weekly dose I would choose Fosamax, for monthly dosing Actonel.
  • Is there a role for calcitonin (Miacalcin) nasal spray, to increase bone density?
    Answer: Only if no other drug can be used, and possibly if the patient has bone pain from a vertebral fracture. Miacalcin does not improve bone density much, and not at all at the hip. It is inferior to all other resorption inhibitors, but better than nothing.
  • When should raloxifene (Evista) be used?
    Answer: This could be a good choice in a patient with osteopenia at the spine but not the hip, who is concerned about breast cancer risk as well. Evista reduces the risk of vertebral fracture (but not hip) and reduces the risk of breast cancer by as much as 60%. It is generally well tolerated but it raises the risk of deep venous thrombosis, unlike bisphosphonates. It can be taken without regard to meals, making it more convenient.

 

Casey Younkin, MD
Southern Illinois University School of Medicine
Springfield, Illinois
Published on November 6, 2012
Updated on November 13, 2012

 

Biosketch
Dr. Casey Younkin is an associate professor on the faculty at Southern Illinois University School of Medicine in Springfield, IL. He has been interested in bone health for many years and is a member of ISCD (International Society of Clinical Densitometry) and ASBMR (American Society for Bone and Mineral Research). His goal is to see every patient with a fragility fracture evaluated and potentially treated, to prevent the next fracture from occurring.