Osteoporosis

Contributors: Marcy Bolster, MDand Alfred Denio, MD

CASE 1

A 68 year old woman presents to your office after retiring from New York City to South Carolina. She is interested in discussing her bone health. She notes that she had a DXA scan performed 3-5 years ago and was told that her bone density was slightly reduced and it was recommended that she take Calcium and Vitamin D supplementation. She is otherwise healthy. She has no specific complaints. She has never sustained a fracture. She denies tobacco or alcohol use. She reports that her mother fell and broke her hip at age 88 years old. Her current medications include Calcium with Vitamin D. Her vital signs are normal and her physical examination is unremarkable.

For her evaluation you request routine laboratory testing to include a comprehensive metabolic panel (CMP), complete blood count (CBC), and serum 25 (OH) Vitamin D level, and all of these tests are normal. A DXA scan is performed and reveals a T-score of L1-L4 to be -2.2, and the right femoral neck T-score is -2.6.

What are your recommendations to this patient?

The DXA scan interpretation reveals that the patient has osteoporosis of the femoral neck T-score of -2.6. She has a family history of osteoporosis with a maternal history of hip fracture. She is thus at increased risk for fracture and should be treated with pharmacologic therapy. The options include anti-resorptive agents such as the bisphosphonates, raloxifene, and denosumab. Raloxifene has been demonstrated to reduce the incidence of vertebral fractures however it does not reduce hip fracture incidence. She is at highest risk for a hip fracture, thus a better choice would be either a bisphosphonate or denosumab therapy. Considerations in the selection of an agent include route of administration (oral or intravenous bisphosphonate therapy or subcutaneous denosumab), frequency of administration and cost to the patient.

CASE 2

A 72 year old woman presents to your office after retiring from New York City to Florida. She is interested in discussing her bone health. She notes that she had a DXA scan performed 3-5 years ago and was told that her bone density was slightly reduced and it was recommended that she take Calcium and Vitamin D supplementation. She is otherwise healthy. She has no specific complaints. She has never sustained a fracture. She denies tobacco or alcohol use. She reports that her mother fell and broke her hip at the age of 88 years old. Her current medications include Calcium 1200 mg daily with Vitamin D 1000 IU daily. Her vital signs are normal and her physical examination is unremarkable.

For her evaluation you request routine laboratory testing to include a comprehensive metabolic panel (CMP), complete blood count (CBC), and serum 25 (OH) Vitamin D level, and all of these tests are normal. The DXA scan interpretation reveals a T-score of L1-L4 to be -1.8, and the right femoral neck T-score is -1.9. The FRAX scores corresponding to these T-scores indicate a 17% and 6.3% ten year probability of a major osteoporotic fracture and hip fracture, respectively.

How would you discuss the meaning of her DXA scan results and of the FRAX scores? What are your recommendations to this patient?

The FRAX tool is a fracture risk assessment tool based on the patient's age, body mass index (BMI), tobacco use, alcohol use, presence of RA, use of glucocorticoids, prior history of fracture, parental history of hip fracture and presence of secondary causes of osteoporosis. The FRAX tool can be applied to patients with osteopenia (T-score between -1.0 and -2.5) who have not been taking medications for osteoporosis (except for Calcium and Vitamin D). It utilizes the femoral neck bone mineral density. Fifty percent of fractures occur in patients with osteopenia, so the FRAX tool is helpful to identify those patients at higher risk for fracture. The FRAX tool provides both a ten year probability prediction for a major osteoporotic fracture (hip, vertebral, forearm, humerus) and for a hip fracture. Thus, two risk predictions are provided for a ten year probability for fracture. For the United States, based on economic factors relating to the cost:benefit ratio, a 20%or higher probability of a major osteoporotic fracture or a 3% or higher probability of a hip fracture at ten years would warrant pharmacologic therapy for osteoporosis.

Thus, this patient is at increased risk for a fracture and should be treated for osteoporosis. She should be offered anti-resorptive therapy with the option of a bisphosphonate or denosumab.

Patient Care

  1. Recognize the approach to the evaluation of a patient with regard to his/her bone health.
  2. Identify the risk factors for osteoporosis.
  3. Recognize patients who should be screened for osteoporosis.
  4. Determine appropriate radiographic testing indicated.
  5. Determine appropriate metabolic lab testing indicated.
  6. Distinguish the appropriate medical management.
  7. Determine the appropriate follow-up for the patient.

Medical Knowledge

  1. Describe the cellular etiology for bone loss in adults.
  2. Recognize the metabolic aberrations involved in secondary causes of bone loss.
  3. Identify medications associated with accelerated bone loss.
  4. Distinguish patients on glucocorticoids who require pharmacotherapy to prevent further loss of bone.
  5. Describe the different pharmacologic therapy options including risks and benefits.
  6. Identify the risks and benefits of pharmacotherapy for osteoporosis including risk to gastrointestinal tract, osteonecrosis of the jaw, renal failure, and atypical femoral fracture.
  7. Identify the contraindications to osteoporosis pharmacotherapy.
  8. Learn how to interpret aDXA scan.
  9. Implement the FRAX tool for fracture risk assessment in appropriate populations.

Interpersonal And Communication Skills

  1. Discuss risk factor modification with a patient.
  2. Discuss fall prevention.
  3. Discuss the results of a DXA scan with a patient.
  4. Discuss the need for appropriate Calcium and Vitamin D supplementation with a patient, including dietary sources.
  5. Discuss the importance of weight bearing exercise for bone health.
  6. Discuss the costs, risks and benefits of osteoporosis pharmacotherapy with a patient and be familiar with issues of costs, risks, and benefits that patients are hearing about from the lay press.
  7. Explain infusion therapies including risks and benefits.
  8. Use web-based resources to educate your patients.
  9. Discuss treatment recommendations with other physicians involved in the care of the patient.

Professionalism

  1. Recognize the importance of patient privacy, informed consent, equal care.
  2. Demonstrate integrity and honesty in discussing patient care issues and management with the patient and family.
  3. Provide adequate time and accessibility to address patient concerns.

Practice-Based Learning And Improvement

  1. Set learning goals in osteoporosis diagnosis and management.
  2. Effectively use DXA scan results to manage patient care decisions and enhance education of the patient and the referring physician.
  3. Integrate and apply the knowledge gained from history and exam, DXA scan reports and plain film radiography to make informed decisions about patient care.
  4. Consider creating a quality improvement project to address bone health issues in patient care and physician management.
  5. Develop a willingness to learn from errors and use errors in a constructive way to learn and to improve the systems for patient care.
  6. Utilize web-based resources and evidence-based medicine to enhance learning about bone health and osteoporosis.

Systems-Based Practice

  1. Identify barriers to the delivery of optimal patient care for patients with low bone mass and offer improved ideas for delivering care.
  2. Behave as a consultant to referring providers to enhance comprehensive care of patients in terms of bone health management.
  3. Demonstrate the ability to collaborate with other health care providers in addressing a patient's bone health including orthopedic surgeons, physical therapists, and gynecologists.
  4. Determine cost-effectiveness of management plans for addressing a patient's bone health.
  5. Implement a cost-effective management plan for a patient with osteoporosis.
  6. Demonstrate awareness of the impact of diagnostic and pharmacologic recommendations on the health care system , insurance companies and patient personal expenditures.

References

  1. Adam G. Elshaug, M.P.H., Ph.D., and Alan M. Garber, M.D., Ph.D. How CER Could Pay for Itself — Insights from Vertebral Fracture Treatments N Engl J Med 2011; 364:1390-1393 April 14, 2011.
  2. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis.BMJ. 2011;19;342.
  3. Calcium and Vitamin D: What You Need to Know - National Osteoporosis Foundation.
  4. Consumer Reports Best Buy Drugs: Drugs to Treat Osteoporosis. September 2013. Accessed May 26th, 2014
  5. Cummings SR, San Martin J, McClung MR et al, Denosumab for prevention of fractures in postmenopausal women with osteoporosis, NEJM 361, 2009: 756-765.
  6. Dennis M. Black, Ph.D., Douglas C. Bauer, M.D., Ann V. Schwartz, Ph.D.,M.P.H., Steven R. Cummings, M.D., and Clifford J. Rosen, M.D. Continuing Bisphosphonate Treatment for Osteoporosis — For Whom and for How Long? N Engl J Med 2012; 366:2051-2053May 31, 2012.
  7. Eisenberg Center at Oregon Health & Science University, Fracture Prevention Treatments for Postmenopausal Women with Osteoporosis: Comparative Effectiveness Review Summary Guides for Clinicians. Rockville (MD): Agency for Healthcare Research and Quality (US): 2007- .
  8. Favus MJ, Bisphosphonates in Osteoporosis, New Engl J Medicine, 2010, pp. 2027-2035.
  9. Grossman JM et al, American College of Rheumatology 2010 Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis, Arthritis Care and Research, 2010, pp. 1515-1526.
  10. Heike A. Bischoff-Ferrari, M.D., Dr.P.H., Walter C. Willett, M.D., Dr.P.H., Endel J. Orav, Ph.D., Paul Lips, M.D., Pierre J. Meunier, M.D., Ronan A. Lyons, M.D., M.P.H., Leon Flicker, M.D., John Wark, M.D., Ph.D., Rebecca D. Jackson, M.D., Jane A. Cauley, Dr.P.H., Haakon E. Meyer, M.D., Ph.D., Michael Pfeifer, M.D., Kerrie M. Sanders, Ph.D., Hannes B. Stähelin, M.D., Robert Theiler, M.D., and Bess Dawson-Hughes, M.D. A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention N Engl J Med 2012; 367:40-49 July 5, 2012.
  11. Hess BJ 1, Johnston MM , Iobst WF , Lipner RS. Practice Practice-based learning can improve osteoporosis care.J Am Geriatr Soc.2013 Oct;61(10):1651-60.
  12. Lewiecki EM, In the clinic: Osteoporosis. Annals of Internal Medicine, 2011, pp. ITCI 2-16.
  13. Lewiecki EM, Managing osteoporosis: Challenges and strategies. Cleveland Clinic Journal of Medicine, 2009, pp. 457-466.
  14. Moyer VA; U.S. Preventive Services Task Force*.Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement.Ann Intern Med.2013;158(9):691- 696.
  15. Murray J. Favus, M.D. Bisphosphonates for Osteoporosis N Engl J Med 2010; 363:2027-2035 November 18, 2010 DOI: 10.1056/NEJMct1004903
  16. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2014. Version 1.
  17. Office of the Surgeon General (US). Rockville (MD): Bone Health and Osteoporosis: A Report of the Surgeon General.2004.
  18. Osteoporosis definition linkaccessed May 26, 2014.
  19. Papapoulos, S., Chapurlat, R., Libanati, C., Brandi, M. L., Brown, J. P., Czerwiński, E., Krieg, M.-A., Man, Z., Mellström, D., Radominski, S. C., Reginster, J.-Y., Resch, H., Ivorra, J. A. R., Roux, C., Vittinghoff, E., Austin, M., Daizadeh, N., Bradley, M. N., Grauer, A., Cummings, S. R. and Bone, H. G. (2012), Five years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first two years of the FREEDOM extension. J Bone Miner Res, 27:694–701.
  20. Prentiss RL, Pettinger MB, Jackson RD,et al. Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study.Osteoporos Int. 2013;24(2): 567- 580.
  21. Reid IR, Bolland MJ. Calcium supplements: bad for the heart?Heart. 2012;98(12):895-896.

Questions

(Answer questions 1 – 5 on a piece a paper. Find Answer Key at the bottom on the page.)

  1. You are asked to see the patient 2 for medical clearance in your hospital's emergency room. She is being admitted to orthopedics because of a right femoral stress fracture found when she developed hip pain after she tripped and fell. She has been taking alendronate for 7 years since you first started it as well as calcium and vitamin D. Her follow up DEXAs showed over 6% improvement in BMD in the lumbar spine, and 4% in the total hip by the end of the 3rd year, and the BMD had remained stable since that time last checked 2 years ago. There were no premonitory symptoms prior to her fall. You review the x-ray which shows a stress fracture below the trochanters. With exception of the pain, she is well with no medical contraindication for her planned procedure. What is the most important recommendation for you to make next?

    1. Change the alendronate to yearly zoledronate since the alendronate failed to prevent a hip fracture.
    2. Order a new DXA to see if there is significant change to warrant changing alendronate to a different treatment.
    3. Order x-ray of the left femur to assess whether that too is fractured
    4. Order tests for secondary causes of osteoporosis since she fractured despite adhering to alendronate therapy.

  2. You advise patient 2 that she is at high risk for fragility fracture and recommend alendronate which she agrees to begin. 3 years later, you repeat a DXA, and her lumbar spine BMD has declined 3.8% while the left total hip is unchanged. She says she has been taking her medication faithfully once weekly on first rising in the morning on an empty stomach with a glass of water waiting at least ½ hour before eating breakfast. Despite taking Vitamin D 1,000 IU daily, her 25-hydroxy Vitamin D level is low 12 ng/ml (normal >30ng/ml). In addition to prescribing additional vitamin D, what else would be most important to order?

    1. Increase alendronate from 70 mg once a week, to twice a week.
    2. TTG.
    3. Ask patient to wait for over an hour after taking her alendronate before eating breakfast.
    4. Increase patient's calcium supplement from 1000 mg daily to 2000 mg daily.

  3. Patient 2 responds to the alendronate 70 mg weekly you prescribed and her bone density improved 8.6% in her lumbar spine and 3.8% in the left total hip over the next 5 years of treatment with a femoral neck T score of -1.4. You see her back and recommend she begin a "holiday" from alendronate 2 years ago since the BMD is much improved. Her follow up DXA off alendronate just done this year shows a stable BMD with no change from 2 years ago and you recommend continuation of the holiday and adequate vitamin D and calcium in the diet. A Vitamin D level is normal. The patient now has developed headaches, jaw claudication and a temporal artery biopsy confirms Giant Cell Arteritis and prednisone is started 60 mg a day. What would be the best next recommendation for her osteoporosis?

    1. Increase calcium supplements to 2000 mg daily and Vitamin D to 50,000 IU weekly
    2. Begin raloxifene daily
    3. Resume alendronate 70 mg weekly
    4. Make no additional treatment recommendation

  4. The 2nd patient returns for follow up and is concerned about your recommendation for 1200mg of daily elemental calcium and 1000 IU of daily vitamin D intake. She has heard that calcium supplements increase the risk of heart disease. What is the evidence that calcium supplements increase the risk of heart disease?

    1. Randomized prospective and retrospective studies have shown increased calcium deposits in coronary arteries in patients taking calcium supplements compared with patients not taking calcium supplements.
    2. Prospective and retrospective studies population studies have demonstrated increased cardiovascular mortality in older patients taking calcium supplements.
    3. Increased cardiovascular risk of taking calcium supplements has been found in patients with hypertension taking calcium channel blockers.
    4. Studies of long term use of calcium supplements have demonstrated higher incidence of kidney stones, kidney disease, and risk of hypertension with its increased risk of cardiovascular mortality.

  5. Patient 2 elects not to take the bisphosphonate you recommended for her. 6 months later she sustains a moderately painful vertebral compression fracture at T-10. She was referred to an orthopedist that week who recommended vertebroplasty. She sees you the next day for an opinion about the procedure versus other management strategies both for her fracture and for her osteoporosis. What would be the 2 most cost effective suggestions you could make regarding her 2 concerns?

    1. Have the vertebroplasty done and begin calcitonin nasal spray
    2. Get an opinion about kyphoplasty rather than vertebroplasty and begin IV ibandronate every 3 months
    3. Wait another 2-4 weeks for the back pain to improve using oral analgesics and begin alendronate 70 mg weekly
    4. Wait another 2-4 weeks for the back pain to improve using oral analgesics and begin teriparatide injections 20 micrograms subcutaneously daily.

Answer Key

  1. The correct answer is C.
  2. Atypical fractures associated with prolonged use of bisphosphonates are rare, but when they occur on one side, there is a high incidence of bilateral femur fractures. This patient should be evaluated immediately for a coexisting stress fracture on the opposite side, which may be asymptomatic (1). While the goal of osteoporosis therapy is to reduce risk of fragility fracture, a fragility fracture does not necessarily indicate treatment failure. Treatment might be changed, but answers A and B would not be the most important next recommendation. D would not be the best answer. One should always consider secondary contributions to metabolic bone disease in the setting of any fragility fracture, but again would not be the most important next recommendation.

    References

  3. The correct answer is B.
  4. When a patient's BMD does not improve with bisphosphonate therapy, it is important to try to determine the contributing factors. Undiagnosed secondary causes of metabolic bone disease are not uncommon reasons. Celiac disease is relatively common in the general population and is often unrecognized. The low vitamin D level despite the supplement suggests the patient is not absorbing the vitamin D normally, a scenario that suggests celiac disease for which the serum TTG would be the best initial screening test. Answer A is not correct as the alendronate approved maximum dose is 70 mg once a week. Answer C is not the best answer. While one can increase the absorption of alendronate by delaying breakfast after the dose, this does not address the vitamin d problem. Likewise, increasing the calcium supplement would not address the vitamin D problem, and higher doses of calcium would be of uncertain benefit to bone strength and may increase risk of kidney stones.

    References

  5. The correct answer is C.
  6. This patient's risk factor profile for sustaining a fragility fracture markedly changed when she had to begin high dose glucocorticoids for giant cell arteritis. She is now again at high risk for losing further bone mass from the steroids and/or sustaining a fragility fracture. The American College of Rheumatology has published guidelines to assist clinicians in the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) referenced below. While it is important to have adequate dietary calcium and vitamin D intake, taking additional calcium and vitamin D above the requirements has not been shown to be helpful and may increase a patient's risk of kidney stones. Raloxifene has not been shown to be effective in either the prevention or treatment of GIOP. Resuming alendronate is the best answer which has been shown to be effective in both the prevention and treatment of GIOP in randomized controlled trials.

    References

  7. The correct answer is B.
  8. Reanalysis of the Women's Health Initiative (a prospective trial designed primarily to look at the risks/benefits of hormone replacement therapy in post-menopausal women but also looked at diet and osteoporosis effects) and other work demonstrates that there is slight but statistically significant increase in cardiovascular events in elderly women taking calcium supplements who were not already on them before the study began compared with women not taking calcium supplements controlling for then known confounding variables. Answer A is not correct as coronary calcification has not been looked at in a randomized fashion. Answer C would not be correct as calcium intake would not affect the mechanism of action of calcium channel blockers. Although taking too much calcium can increase a person's risk for urinary calculi, there are no studies showing increased incidence of hypertension in patients taking calcium supplements.

    References

  9. The correct answer is C.
  10. The back pain associated with an osteoporotic vertebral compression fracture will usually improve greatly within several weeks without specific therapy and vertebral augmentation procedures such as vertebroplasty or kyphoplasty are usually not necessary. The utilization and timing of these procedures are controversial but since most patients improve without them, they are generally reserved for patients with incapacitating pain that fails to respond to a trial of conservative management. Most clinicians consider intranasal calcitonin to have minimal evidence for efficacy. IV ibandronate is expensive and in prospective clinical trials has not been shown to reduce the incidence of hip fractures and as such is not considered as effective as other less expensive alternatives. Teriparatide is a very effective treatment for osteoporosis and in controlled trials appears to be slightly more effective than alendronate, but is an order of magnitude more expensive than generic alendronate and as such would not be as cost effective as alendronate.

    References

Last updated February 2015.