Hamdy, Ronald C. MD, FRCP, FACP; Baim, Sanford MD, FACR; Broy, Susan B. MD, FACP, FACR, CCD; Lewiecki, E. Michael MD, FACP, FACE; Morgan, Sarah L. MD, MS, RD, FADA, FACP, CCD; Tanner, S. Bobo MD; Williamson, Howard F. MD, FACOG
From the of Department of Geriatric Medicine and Gerontology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN; Department of Clinical Medicine, Chicago Medical School, Chicago, IL; Department of Medicine, University of Colorado Health Sciences; New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, and Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM; Department of Nutrition Sciences and Medicine, University of Alabama at Birmingham, Birmingham, AL; Rheumatology and Allergy Division, Vanderbilt University Medical Center, Nashville, TN; and Cullman OBGYN PC, Cullman, AL.
Reprint requests to Ronald C. Hamdy, MD, FRCP, FACP, Department of Geriatric Medicine and Gerontology, Quillen College of Medicine, East Tennessee State University, Box 70429, Johnson City, TN 37614. Email: firstname.lastname@example.org
The views expressed in this article are solely those of the authors and are only intended for guidance. They do not substitute clinical judgment, which must be tailored to the individual patient and made by healthcare providers. Neither the Southern Medical Association nor the Southern Medical Journal endorse or condone statements made in this manuscript.
Dr. Morgan received honoraria as a consultant from Amgen and Eli Lilly, received an honorarium as a consultant/speaker from Genentech, and received an honorarium for teaching bone density classes from the International Society for Clinical Densitometry. Dr. Williamson received honoraria as a speaker from Eli Lilly and Novartis. Dr. Broy received honoraria as a consultant and speaker for Amgen, Eli Lilly, Novartis, and Warner Chilcott. Dr. Tanner received honoraria as a speaker for Genentech/Roche, Eli Lilly, Novartis, and Amgen. Dr. Lewiecki received grant and research support from Amgen, Eli Lilly, Novartis, Merck, Warner Chilcott, Genentech, and other support from Amgen, Eli Lilly, Novartis, and Genentech for involvement with their respective scientific advisory boards speakers' bureaus. He is on the board of directors, International Society for Clinical Densitometry. Dr. Hamdy has received honoraria as a speaker/consultant for Amgen, Eli Lilly, Proctor & Gamble, and Novartis.
Accepted June 17, 2010.
* With appropriate care, osteoporosis can be prevented; and when present, it can be easily diagnosed and managed.
* It is recommended, whenever possible, to test patients at risk for osteoporosis with DXA measurement of at least two skeletal sites—usually the lumbar spine and proximal femur.
* The minimum recommended laboratory tests for patients diagnosed with osteoporosis or osteopenia include complete blood count, comprehensive metabolic profile, and serum vitamin D (25-hydroxyvitamin D) level. Other tests may be appropriate for patients with special considerations.
* Medications are available to manage osteoporosis and reduce fracture risk, and there are many lifestyle changes individuals should use to help manage osteoporosis.
* Every adult should be advised on the importance of adequate calcium and vitamin D intake, good nutrition, and healthy lifestyle to enhance skeletal health.
Osteoporosis is a common condition characterized by a reduced bone mass, altered bone architecture, and increased fracture risk.1,2 It affects both genders, and predominantly those over the age of 50 years. It is now easily diagnosed, and a number of medications are available to significantly reduce the risk of fractures. The estimated economic impact of osteoporosis-related fractures is staggering: $17 billion was spent in 2005 alone.3 The prevalence of osteoporotic fractures exceeds the combined prevalence of breast cancer, stroke, heart failure, and myocardial infarction.4–6 Unlike most of these conditions, however, the prognosis of osteoporosis is good if adequately treated in a timely manner. Unfortunately, osteoporosis still remains underdiagnosed and undertreated, even after patients sustain low-trauma hip fractures.7–17
It is possible that lack of time rather than lack of interest is the main cause of the underdiagnosis and undertreatment of osteoporosis. Also, the availability of multiple guidelines may hinder rather than help primary care providers, especially as most of these guidelines are geared towards specialists rather than generalists and therefore tend to be comprehensive and all-inclusive. The authors therefore feel there is a need to consolidate and simplify the available guidelines; and to develop an algorithm that busy primary care clinicians can use to diagnose and manage osteoporosis (Fig.).
Fig. Osteoporosis Al...Image Tools
The diagnosis of osteoporosis can be established by:
* The presence of a fragility fracture—a fracture sustained spontaneously, after minimal trauma, or after a fall from a height not exceeding the body height. This includes vertebral compression fracture detected by spine imaging such as radiography, or Vertebral Fracture Assessment (VFA) by dual x-ray absorptiometry.
* A T-score of −2.5 or less with bone mineral density (BMD) testing of the proximal femur(s), lumbar spine, or one-third (33%) radius by DXA, using the guidelines established by the World Health organization (WHO).
Identifying At-Risk Patients
As osteoporosis is an asymptomatic condition until a fracture occurs, bone density testing is recommended in the following patients:
* women aged 65 years and older18–21;
* men aged 70 years or older18,19;
* postmenopausal women or men age 50 years and older with clinical risk factors for fracture,18,19 including history of hip fracture in one of the biological parents; current cigarette smoking; current alcohol abuse, as defined by 3 or more drinks a day; and a diagnosis of rheumatoid arthritis;
* adults who have sustained a fracture after age 50 years16,19;
* chronic glucocorticoid therapy (≥5 mg/d of prednisone or equivalent for ≥3 months)16,21,22;
* adults with a medical disease or condition that may be associated with a low bone mineral density (BMD) or bone loss16,18 (Tables 1 and 2);
* adults on medication that may induce bone loss16,18 (Table 3).
Selecting a Bone Density Test
It is recommended, whenever possible, to test patients at risk for osteoporosis with DXA measurement of at least two skeletal sites—usually the lumbar spine and proximal femur. When one or both of those skeletal sites cannot be measured due to structural abnormalities (eg, osteophytes, vertebral compression fractures, previous surgery involving the lumbar spine, or previous surgery or severe deformity of the hips) or other reasons (eg, body weight exceeding DXA table specifications or inability to lie on the DXA table), then the forearm (one-third radius) should be measured.
If the patient reports a height loss of 2 or more from the maximum historical height, a spine imaging study such as the VFA is recommended in addition to the BMD measurement by DXA. The presence of a vertebral compression fracture in the absence of significant trauma is consistent with a diagnosis of osteoporosis and is a significant independent risk factor for future fractures.19
Epidemiological studies have shown that peripheral bone density measurements such as quantitative ultrasound (QUS) and peripheral DXA of the heel can be used to predict fracture risk.23 However, with the exception of the one-third radius, peripheral BMD measurements cannot be used for diagnostic purposes. It is also not uncommon for patients to have a “normal” T-score with QUS of the heel and yet have osteopenia or osteoporosis with DXA testing of the lumbar spine and hips. As the age-associated pattern of decrease in BMD is different in different bones–very slow in the heel and much more rapid in the lumbar spine—the rate of detection of osteoporosis or osteopenia would be much lower in patients having scans of the heel performed and higher in patients having the lumbar spine analyzed.
There is concern that if non-DXA technologies are used exclusively in clinical practice, many patients who could benefit from therapy will not be identified. However, if peripheral measurements suggest osteoporosis, a central DXA is indicated, and is likely to be reimbursed by Medicare for the purposes of establishing baseline scan BMD values that may be helpful in monitoring the effect of therapy.24
Understanding DXA Scan Results
BMD measured by DXA is calculated by dividing the bone mineral content (g) by the surface area (cm2) of the bones scanned. The patient's BMD is then compared to that of two reference populations:
* a young, healthy adult population of the same sex. The number of standard deviations between the patient's BMD and the mean BMD of this population is referred to as the T-score.
* An age- and sex-matched population. The number of standard deviations between the patient's BMD and the mean BMD of this population is referred to as the Z-score.
If the lowest T-score of the femoral neck, total hip, or lumbar vertebrae (or one-third radius, if measured) is −2.5 or lower, or if there is a past history of fragility fracture, the patient has osteoporosis. This patient should be investigated for factors contributing to osteoporosis and considered for treatment to reduce fracture risk.18,19
If the lowest T-score is between −1.0 and −2.5, and there is no past history of fragility fracture, the patient has osteopenia (low bone mass). This patient may benefit from fracture risk assessment using VFA and FRAX®25:
* If the VFA shows a vertebral compression fracture and the patient denies any back trauma, the diagnosis is osteoporosis, and treatment should be considered.
* The WHO FRAX® estimates the 10-year probability (expressed as a percentage) of major osteoporotic fracture (spine, hip, proximal humerus, or distal forearm) and the 10-year probability of hip fracture. At present, the FRAX®, can only be applied to untreated patients. The NOF has issued guidelines to determine the 10-year fracture probability at which it is likely to be cost-effective to treat with a pharmacological agent to reduce fracture risk: 20% and above for major osteoporotic fracture or 3% and above for hip fracture.18 Healthy lifestyle and good nutrition are indicated for all patients, regardless of fracture risk. In addition, efforts to reduce the frequency of falls or the impact of falls may reduce the risk of fracture, especially in older people.
If the lowest T-score is −1.0 or higher, the patient has a normal bone density.
Recommending Laboratory Tests Prior to Initiating Treatment
The following laboratory tests are the minimum recommended for patients diagnosed with osteoporosis or osteopenia in order to identify secondary causes and aid in determining optimum treatment:
* complete blood count, to detect the presence of anemia, macrocytosis or microcytosis;
* comprehensive metabolic profile, to assess serum calcium level; renal and hepatic functions; and abnormalities that may be suggestive of malnutrition (low albumin, low total protein, low cholesterol), or multiple myeloma (elevated serum protein);
* serum vitamin D (25-hydroxyvitamin D) level to detect hypovitaminosis D; and
* additional tests that may be appropriate for some patients include: serum parathyroid hormone (intact molecule); tissue transglutaminase or anti-endomysial antibodies; erythrocytic sedimentation rate; serum or urine protein electrophoresis; serum bone-specific alkaline phosphatase; serum C-telopeptide (CTX); serum or urine N-telopeptide (NTX); serum P1NP; thyroid-stimulating hormone (TSH); serum phosphorus; and 24-hour urinary calcium, creatinine, sodium, and cortisol.
The ultimate decision as to whether to treat and how to treat a patient should be based on all available clinical information. Therefore, these guidelines are merely aids in helping clinicians reach these decisions.
Determining Who Should be Considered for Treatment
* Those who have sustained fragility (low energy or low trauma) fracture of the hip or spine;
* Those who have densitometric evidence of osteoporosis (lowest T-score of −2.5 or less at the femoral neck or lumbar spine) after evaluation for secondary causes of osteoporosis;
* Those who have a densitometric diagnosis of osteopenia and a FRAX® 10-year probability of major osteoporotic fracture of 20% or more or 10-year probability of hip fracture of 3% or more.18
Medications are available to manage osteoporosis and reduce fracture risk (Table 4). Additionally, there are many lifestyle changes individuals should use to help manage osteoporosis. Some of these include:
* adequate calcium and vitamin D intake. The NOF recommends at least 1,200 mg of calcium and 800 to 1,000 IU of vitamin D daily for adults 50 years of age and older. It's possible that the recommended maintenance vitamin D dose is too low and may need to be increased in the future.35
* Good nutrition including adequate protein intake (especially important in the elderly);
* smoking cessation;
* cessation of alcohol abuse;
* resistive and endurance physical exercises;
* back extension exercises36
In order to monitor a patient's response to medication and lifestyle changes, follow-up DXA scans are appropriate. The timing of the follow-up DXA scan depends on the expected change in BMD, and the precision and least significant change (LSC) of the DXA center where the scans are performed. A repeat DXA scan 1–2 years after treatment is initiated should be considered. Satisfactory responses to treatment include an increase in BMD exceeding the LSC or a change in BMD within the LSC bracket. To calculate a technologist's precision, clinicians can utilize the ISCD Advanced Precision Calculating Tool, available at http://www.iscd.org/visitors/pdfs/EnglishPrecisionCalculatingTool-Advanced.xls.
Changes in the level of bone turnover markers in the serum or urine may also be used to monitor the patient's response to treatment. When bisphosphonates are administered, a reduction of 40% or more in the markers of bone resorption suggests a positive response. Treatment-induced changes in bone markers also may be predictive of BMD response and fracture-risk reduction.37
Noncompliance is common and associated with more fractures. In a study on bisphosphonate adherence, at 50% compliance with bisphosphonates, fracture rate was no different than in those who were on no medication.38 Best fracture reduction was seen with 90% compliance. Another study on a large database39 demonstrated that only 54.6% of patients on weekly bisphosphonate and 36.9% on daily were compliant (defined only as taking one dose monthly) at one year.
Deciding When to Refer to a Specialist
Clinicians providing primary care may wish to consider referring the following patients to specialists:
* patients not responding to treatment;
* patients with the presence of fragility fractures and normal BMD;
* patients with very low BMD;
* patients with concerns about the safety of prescribed medications; and
* patients with complex clinical circumstances.
Patients with osteopenia and a FRAX® score below the threshold recommended by the NOF to initiate treatment may be candidates for prevention. The mainstay of prevention is lifestyle modification, as outlined in the section on treatment. Some medications are also approved for the prevention of osteoporosis and are listed in Table 5.
Every adult should be advised on the importance of adequate calcium and vitamin D intake, good nutrition, and healthy lifestyle to enhance skeletal health. The assessment of fracture risk includes BMD testing by DXA in appropriate patients. Patients who should be considered for pharmacological therapy to reduce fracture risk are those with osteoporosis by virtue of having a T-score of −2.5 or less or having a history of hip fracture or vertebral fracture, and those with a T-score between −1.0 and −2.5 who have a high fracture probability using FRAX®. Treatment decisions should be based on all available clinical information. Patients should be monitored to assure that the expected treatment effect is achieved and to address side effects and other patient concerns.
We thank Ms. Lindy Russell for editorial assistance, and Dr. Bess Dawson-Hughes, Dr. Wesley Eastridge, and Dr. Jim Holt for their contributions.
1.Consensus Development Conference 1991: prophylaxis and treatment of osteoporosis. Am J Med 1991;90:107–110.
2.NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001;285:785–795.
3.Burge RT, Dawson-Hughes B, Solomon D, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 2007;22:465–475.
4.Riggs BL, Melton LJ III. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 1995;17(5 suppl):505S–511S.
7.Hooven F, Gehlbach SH, Pekow P, et al. Follow-up treatment for osteoporosis after fracture. Osteoporosis Int 2005;16:296–301.
8.Siris ES, Bilezikian JP, Rubin MR, et al. Pins and plaster aren't enough: a call for the evaluation and treatment of patients with osteoporotic fractures. J Clin Endocrinol Metab 2003;88:3482–3486.
9.Castel H, Bonneh DY, Sherf M, et al. Awareness of osteoporosis and compliance with management guidelines in patients with newly diagnosed low-impact fractures. Osteoporosis Int 2001;12:559–564.
10.Gold DT, Silverman SL. Compliance with osteoporosis medications: challenges for healthcare providers. Medscape Ob/Gyn Womens Health
. 2005. Available at: www.medscape.com/viewarticle/503214
. Accessed September 26, 2006.
11.Gass M, Dawson-Hughes B. Preventing osteoporosis-related fractures: an overview. Am J Med 2006;119(4 suppl 1):S3–S11.
12.Edwards BJ, Bunta AD, Madison LD, et al. An osteoporosis and fracture intervention program increases the diagnosis and treatment for osteoporosis for patients with minimal trauma fractures. Jt Comm J Qual Patient Saf 2005;31:267–274.
13.Stafford RS, Drieling RL, Johns R, et al. National patterns of calcium use in osteoporosis in the United States. J Reprod Med 2005;50(suppl 11):885–890.
15.U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, U.S. Department of Health and Human Services, Office of the Surgeon General, 2004.
16.Elliot-Gibson V, Bogoch ER, Jamal SA, et al. Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: a systematic review. Osteoporos Int 2004;15:767–778.
17.Jennings LA, Auerbach AD, Maselli J, et al. Missed opportunities for osteoporosis treatment in patients hospitalized for hip fracture. J Am Geriatr Soc 2010;58:650–657.
18.National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis
. Washington, DC, National Osteoporosis Foundation, 2008. Available at: www.nof.org/physguide
. Accessed February 18, 2010.
20.North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of the North American Menopause Society. Menopause 2006;13:340–367.
21.U.S. Preventive Services Task Force. Screening for osteoporosis in postmenopausal women: recommendations and rationale. Ann Intern Med 2002;137:526–528.
22.Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496–1503.
24.Cazzaniga ME, Mustacchi G, Pronzato P, et al; NORA Study Group. Adjuvant systemic treatment of early breast cancer: the NORA study. Ann Oncol 2006;17:1386–1392.
25.Kanis JA, Johnell O, Oden A, et al. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008;19:385–397.
26.Cummings SR, Black DM, Thompson DE. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998;280:2077–2082.
27.Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 1999;282:1344–1352.
28.McClung MR, Geusens P, Miller PD, et al; Hip Intervention Program Study Group. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 2001;344:333–340.
29.Chesnut CH, Skag A, Christiansen C, et al; Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE). Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 2004;19:1241–1249.
30.Black DM, Delmas PD, Eastell R, et al; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809–1822.
31.Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282:637–645.
32.Chesnut CH III, Silverman S, Adriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence of Osteoporotic Fractures study. Am J Med
33.Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434–1441.
34.Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. New Engl J Med 2009;361:756–765.
35.Sinaki M. Critical appraisal of physical rehabilitation measures after osteoporotic vertebral fracture. Osteoporos Int 2003;14:773–779; Erratum in: Osteoporos Int 2006;17:1702.
36.Heaney RP. The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 2005;97:13–19.
37.Garnero P, Delmas PD. Biochemical markers of bone turnover in osteoporosis, in Marcus M, Feldman D, Kelsey J (eds): Osteoporosis San Diego, Academic Press, 2001, vol 2, ed 2, pp 459–477.
38.Siris ES, Harris ST, Rosen CJ, et al. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 2006;81:1013–1022.
39.Ettinger MP, Gallagher R, Amonkar M. Medication persistence is improved with less frequent dosing of bisphosphonates but remains inadequate. Arthritis Rheum 2004;50(suppl):S513–S514. [Abstract 1325].
Product Code: SMJ10-10A
Algorithm for the Management of Osteoporosis
October CME Questions
1. The following is/are risk factors for osteoporosis:
A. Early surgical menopause
B. Cigarette smoking
C. Low daily calcium intake
D. A & C
E. All of the above
2. Screening DXA scans are recommended in the following instances:
A. Women aged 65 years and older
B. Men aged 70 years and older
C. Women and men aged 50 years and over with risk factors for osteoporosis
D. A & B
E. All of the above
3. The FRAX score:
A. Estimates the 10-year probability of sustaining an osteoporotic fracture of the hip or other major bones
B. Should be done in patients with osteopenia
C. Should not be done in patients who have been treated for osteoporosis
D. A & B
E. All of the above
Online CME Request Form
October 2010 CME Questions — Answer Key
1. E, 2. E, 3. E
algorithm; FRAX; osteopenia; osteoporosis; vitamin D
Figure. CME Submissi...Image Tools
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