Clinical Practice Guideline

for

OSTEOPOROSIS

Developed for the

Aerospace Medical Association

by their constituent organization

American Society of Aerospace Medicine Specialists

 

Overview: Osteoporosis is the most prevalent disease of bone, affecting an estimated 10 million Americans.  It is a “disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and an increase in fracture risk.”  Osteoporosis is caused by a combination of increased bone resorption and inadequate bone formation which result in deterioration of trabeculae.  Although it may be of clinical significance in men, osteoporosis is four times as common in women and is especially active in the first ten post-menopausal years.

 

The initial clinical presentation of osteoporosis typically is a fracture which may be symptomatic or occult.  In the latter case, the typical finding is one or more spinal compression fractures on radiographs taken for other reasons.  Fractures (especially hip, forearm, and spine fractures) also account for most of the morbidity of the disease, which is further complicated in many cases by subsequent poor healing.  Consequently, patients may have chronic pain, postural/skeletal deformities, and in advanced cases restricted respiratory function from thoracic deformities.  In the elderly population, osteoporotic fracture of the hip is frequently a pre-terminal event.  With occasional exceptions, most of these problems will occur after a normal flying career has ended, but the rapidity of bone loss immediately after menopause in women predisposed to osteoporosis means that prophylaxis concerns will routinely arise during a flying career.

 

Table 1.  Risk factors for osteoporosis

Personal history of adulthood fracture

First-degree relative with history of adulthood fragility  fracture

Current cigarette smoking

Low body weight (less than 58 kg [127 lb])

Corticosteroid therapy greater than 3 months.

Female sex

Estrogen deficiency (menopause [especially before age 45 years], bilateral oophorectomy, prolonged premenopausal amenorrhea [greater than one year])

Caucasian or Asian race

Age

Lifelong low calcium intake

Alcoholism

Inadequate physical activity

 

The commonest form of osteoporosis appears to be caused by low estrogen state (e.g., postmenopausal, bilateral oophorectomy); additional risk factors which increase the likelihood or severity are listed in Table 1.  Osteoporosis may also be secondary to a variety of other medical conditions.  Certain diseases like hyperthyroidism, hyperparathyroidism, hypogonadism, and Paget’s disease, any of which might reasonably be encountered in an aviator, can cause or mimic osteoporosis.  A number of other diseases are in the broader differential diagnosis, including acromegaly, Cushing’s syndrome, osteomalacia, and malignancies such as lymphoma and multiple myeloma.  Furthermore, the use of certain medications such as heparin, glucocorticoids, vitamin A, and chemotherapeutic agents may occasionally be complicated by bone loss.

 

To identify osteoporosis before fractures occur, screening for this disease is important.  Current guidelines from the National Osteoporosis Foundation, the American Association of Clinical Endocrinologists, the National Institutes of Health, the U.S. Preventive Services Task Force and others agree that women greater than 65 years old, women with a history of postmenopausal fracture, or any adult with a fracture occurring in the absence of sufficient trauma should be screened for osteoporosis.  Recently revised guidelines also recommend that postmenopausal women with risk factors for fracture be considered candidates for screening.  To clarify the important risk factors in postmenopausal women, the Osteoporosis Risk Assessment Instrument (ORAI) (based on age, weight and estrogen use) and the Simple Calculate Osteoporosis Risk Estimation (SCORE) (based on race, fracture history, rheumatoid arthritis comorbidity, age, weight and estrogen use) surveys have been developed and validated for yielding good indications for screening bone density measurement.

 

In the military aviator population, one is most likely to encounter perimenopausal women with concerns driven by a family history of postmenopausal osteoporosis.  Consensus on how to proceed in this population has not been reached.  However, a 43-year-old, Caucasian female weighing 120 pounds with irregular menstrual cycle and a family history of osteoporosis may benefit from screening and, if appropriate, treatment.  The health care provider must exercise clinical judgment on individual assessments.

 

Dual-energy x-ray absorptiometry (DEXA or DXA Scan) is the most popular method of densitometry and is readily available in most medical communities for osteoporosis screening.  DEXA scan results have been well-correlated with fracture risk.  The results of a DEXA scan are reported using T-scores and Z-scores.  T-scores are standard deviations from a normal young healthy population mean.  Z-scores are standard deviations from an age-matched, sex-matched, and sometimes race-matched population mean.  Women with a T-score of -2.5 or lower (i.e., a larger negative number) are said to have osteoporosis, and those with a T-score between -1.0 and -2.5 are said to have osteopenia.  Osteopenia should not be thought of as a separate disease, but an early form of osteoporosis, with the significant caveat that some women in the osteopenic range may not progress to osteoporosis.

 

In addition to bone densitometry, laboratory screening for underlying causes of osteopenia and osteoporosis has also been widely supported, although a precise algorithm has not been uniformly endorsed.  The utility of a workup depends on the clinical scenario.  For instance, it makes little sense to pursue an exhaustive evaluation to identify a secondary cause of early-stage osteopenia in a 45-year-old perimenopausal female who was screened because of a positive family history; after all, it was the patient’s underlying risk that prompted the screening in the first place.  On the other hand, a fragility fracture which leads to the identification of osteoporosis in a male or premenopausal female should be thoroughly evaluated.  A reasonable approach would be to evaluate individuals initially diagnosed with osteoporosis with a complete blood count, serum chemistries (electrolytes, blood urea nitrogen, creatinine, calcium, phosphorous, total protein, albumin, liver transaminases and alkaline phosphatase), 25-hydroxyvitamin D levels, urinalysis, and 24-hour urine for calcium excretion and creatinine.  Additional studies should be driven by history and clinical exam and may include thyroid function tests, parathyroid hormone, serum testosterone (men), serum estradiol, urine free cortisol, or others.  For individuals who fail to respond to alendronate therapy, biochemical markers of bone metabolism (specifically urinary N-telopeptide crosslinks) should be evaluated.

 

Current strategies in osteoporosis treatment are increasingly focusing on preventing and mitigating the loss of bone in the post-menopausal women, and therapy is generally tailored to the bone density as determined by DEXA scan.  All women can probably benefit from a healthy diet high in calcium, supplementation with calcium and with vitamin D, smoking cessation (when applicable), moderation of alcohol (if consumed), and regular weight-bearing exercise of any intensity.

 

As noted earlier, osteopenia and osteoporosis are best viewed as a continuum.  Rather than distinguishing between the two entities, prophylaxis recommendations are based on a T-score of -2.0 or worse, though a score of -1.5 may be used as a treatment threshold if multiple risk factors are present.  Both hormone replacement therapy (HRT), with estrogen alone or combined with a progestin, and bisphosphonates have been considered first-line therapies for the management and treatment of osteoporosis.  However, recent results from the Women’s Health Initiative have raised concerns about breast cancer and cardiovascular risks due to HRT.  For this reason, bisphosphonate therapy is the preferred first-line therapy in most cases.

 

Alendronate is a bisphosphonate approved by the US Food and Drug Administration (FDA) for the prevention and treatment of osteoporosis in postmenopausal women and is on the Official Air Force Approved Aircrew Medication List.  Common side effects of alendronate for which aircrew should be monitored when using this medication include thoracic and abdominal pain (due to esophageal or gastric ulcerations), nonspecific gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation), melena, hematochezia, musculoskeletal pain, headache, and allergic reaction.  These risks are minimized by technique of administration, which is outlined below.  Teriparatide (Forteo®), a recombinant parathyroid hormone, is also available; unlike bisphosphonate therapy, this agent consistently induces regrowth of bone.  Major disadvantages of parathyroid hormone, besides expense and the necessity for refrigeration, include consistent elevations of serum calcium (with excursions into the abnormal range about 11% of the time), and the risk of inducing osteosarcoma.  This agent is usually reserved for those with progressive failure of bisphosphonates, and for those with extreme levels of osteoporosis, and as such is rarely indicated.  Therapy with teriparatide is not waiverable in the military.  Calcitonin therapy is very rarely employed; the usual indication is pain control in the face of recurrent fragility fractures, and thus neither the condition nor the therapy would be waiverable.

 

Monitoring the efficacy of osteoporosis treatment is medically and aeromedically important, though there is some disagreement on how to monitor appropriately.  The commonly accepted method to monitor sufficiency of treatment is to repeat bone densitometry at two year intervals.  Some patients will experience an increase in bone density on bisphosphonate therapy, but in general treatment is considered satisfactory if it results in arrest of bone loss.  DEXA scanning should include the lumbar spine and bilateral hips.  While bone density measurement of the left hip can be acceptable for making the diagnosis of osteoporosis, assessment of therapy requires serial measurement of lumbar spine and total hip scores.  The lumbar spine value is based on AP lumbar spine, not the lateral.  (The same is true for initial diagnosis; unlike the left hip T-score, the lateral spine T-score is not useful for diagnosis either.)  Absolute BMD, rather than T-score, is assessed for response to therapy; a loss of 4% of hip density, and/or 5% of spine density, is considered significant.  If this happens despite alendronate therapy, work-up should address poor absorption of the drug, and include re-evaluation of vitamin D levels.

 

Aeromedical Concerns: While certain aviation career fields, such as loadmaster or aeromedical evacuation crewmembers, routinely involve weight bearing labor, any aircrew member may be called upon for physical exertion.  All aircrew have the potential need to quickly egress their aircraft, and help others do so as well.  In many cases the egress route may involve climbing up or down, with drops or falls of several feet, and may necessitate the rapid movement of heavy objects or assistance to other crew members.  These conditions would further increase the likelihood of pathologic fractures in an osteoporotic aviator.  Furthermore, a fracture while egressing emergently would pose an additional threat to the safety of the injured aviator and other aircrew by delaying evacuation.

 

In high-performance aircraft, aviators have a known, increased risk of cervical and lumbar injury due to the large forces experience in high “G” maneuvers.  No body of data exists regarding the response of osteopenic/osteoporotic aviators in this environment due to a paucity of affected individuals who have been exposed, although anecdotal cases have certainly occurred (e.g., symptomatic vertebral fracture during initial centrifuge training in an osteoporotic male).  It is almost certain that acceleration stresses on bone tissue weakened by osteoporosis would result in a higher incidence of these types of injuries.  A fragility fracture occurring under high-G conditions could even result in a catastrophic mishap.

 

Alendronate is a reasonably effective drug, and the risk of side effects is minor as long as proper technique of administration is followed.  It should be taken on a fasting stomach with water only, and no other food or beverage should be consumed for an hour after medicating to prevent inactivation of the drug.  To avoid esophageal damage, an upright posture needs to be maintained for at least an hour after ingestion.  (The drug’s inactivation by food can be useful; to further avoid the risk of esophageal ulceration, and the need to continue remaining upright, individuals are typically advised to eat a snack or meal an hour after taking the drug.)  In high-performance aircraft some concern exists about the risk of inducing regurgitation of gastric contents due to G-suit abdominal compression, negative Gz forces, and reclined seating.  In order to minimize this risk, it is recommended that high-performance aviators dose alendronate on a day when no flying is planned.  If conflict with the flying schedule is unavoidable, the aviator should medicate at least 30-60 minutes prior to flying, and should eat a snack just before taking off, which will effectively neutralize any remaining drug.

 

Medical Work-up: The required work-up and documentation for waiver consideration of osteoporosis includes a good history to include any symptoms, family history, all medications, activity level, and menopausal status.  Necessary labs include CBC, electrolytes, BUN, creatinine, phosphorus, calcium, total protein, albumin, liver transaminases, and alkaline phosphatase.  Bone density measurements are also important, particularly of the hip and lumbar spine.

 

Aeromedical Disposition:

 

Air Force: Waiver will not be considered for initial flying training in most cases.  If an underlying cause for osteoporosis was identified, the underlying disease must be eligible for waiver, and must be treated effectively enough that the osteoporotic process is reversed.  For trained aviators, the finding of osteopenia or osteoporosis, whether or not of a degree that requires prophylaxis, would not require airframe restriction, but the occurrence of a fragility fracture would require restriction from high-performance and ejection seat aircraft.  For non-pilot aircrew, the variety of duties requires individual consideration; for instance, severe osteoporosis or the occurrence of a fragility fracture would contraindicate parachute duty.  For aviators requiring alendronate therapy, response to therapy and waiver status should be reassessed every two years.  For those with osteopenia not requiring therapy (e.g., T-score <2.0), BMD should be initially reassessed at two years; if stable, recommend waiver duration of three to five years.

 

Army: Osteoporosis has not proved to be very significant in the Army aviation population.  It has no Army APL of its own, but is discussed in the Backache and Osteoarthritis APL.  Chronic medication for back pain beyond acetaminophen and NSAIDs are rarely considered for waiver, however waiver for chronic bisphosphonate therapy may be considered on an individual basis.

 

Navy: The US Navy waiver guide does not include protocol specific for osteoporosis.  However, the condition and medication usage has been waivered on a case-by-case basis.

 

Civilian: Osteoporosis and its treatments are not disqualifying unto themselves.  An acute fracture would be disqualifying until the fracture stabilizes and the pain can be treated without narcotic analgesics.  If as a result of a fracture the airman is physically limited in any way the airman may require a medical flight test and ultimately a Statement of Demonstrated Ability.  The medications used, especially Alendronate, for the prophylaxis of osteoporosis is acceptable.  In the United States aircrew do not require medical certificates. It is not a FAA requirement as part of medical certification that airmen must be able to escape from the aircraft. 

 

Waiver Experience:

 

Air Force: A review of AIMWTS revealed 26 cases of osteoporosis/osteopenia, 2 FC I/IA, 12 FC II, and 12 FC III.  Of the 26 cases, 7 were disqualified; 1 FC I (history of cerebellar tumor) 2 FC II (1 for multiple medical problems and 1 for vertebral fracture with significant pain) and 4 FC III (2 for use of unapproved medications, one for inadequate vision and 1 for bad headaches). Both of the disapproved for medications were for drugs now approved.

 

Army: The Army’s Aeromedical Epidemiological Data Registry was queried for the period of 1960 to 2009.  This case series contains 160,000 individuals.  The series included 10,200 females.  This is a long span of time during which aeromedical policy has evolved.  There were 4 cases of osteoporosis.  Of those, 3 were retained in aviation.  Of these 2 were rated aviators.  Note that flight applicants were included in the data set, but not included as rated aviators.

 

Navy: No numbers to report at this time.

 

Civilian: The current Path Code system has the same code for Lyme Disease and for Osteoporosis.  Those numbers as of August 2009 are: 205 for first class, 172 for second class and 666 for third class

 

ICD 9 Codes for Osteoporosis

733.00

Osteoporosis, unspecified

733.01

Osteoporosis, postmenopausal

733.02

Idiopathic osteoporosis

733.03

Disuse osteoporosis

733.09

Other osteoporosis

733.90

Osteopenia

 

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References:

 

American Association of Clinical Endocrinologists. 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis. Available at: http://www.aace.com/clin/guidelines/osteoporosis2001.pdf. Accessed Mar 2006.

 

Cadarette, SM.  Evaluation of Decision Rules for Referring Women for Bone Densitometry by Dual Energy X-ray Absorptiometry.  Journal of the American Medical Association 2001 Jul 04; 286(1):  57-63.

 

Cadarette SM, et al.  Development and Validation of the Osteoporosis Risk Assessment Instrument to Facilitate Selection of Women for Bone Densitometry.  CMAJ 2000; 162:  1289–94.

 

Crandall C.  Laboratory Workup for Osteoporosis: Which Tests Are Most Cost-effective?  Postgraduate Medicine 2003 Sep; 114(3):  35-44.

 

Delaney MF.  Strategies for the Prevention and Treatment of Osteoporosis During Early Menopause.  American Journal of Obstetrics and Gynecology 2006;194,S12-23.

 

Finkelstein JS.  Overview of Osteoporosis in Men.  UpToDate Online 14.1 2005 NOV 28.  http://www.utdol.com/utd/content/topic.do?topicKey=minmetab/20928&type=A&selectedTitle=3~157

 

Indications and Reporting for Dual-Energy X-ray Absorptiometry: The Writing Group for the ISCD Position Development Conference: International Society for Clinical Densitometry Position Development Conference, Cincinnati, OH, July 25-27, 2003.  Journal of Clinical Densitometry 2004 Spring 7(1):37-44.

 

Kanis JA, et al.  The Diagnosis of Osteoporosis. Journal of Bone & Miner Research 1994 Aug;9(8):1137-41.

 

Lane NE.  Epidemiology, Etiology, and Diagnosis of Osteoporosis.  American Journal of Obstetrics and Gynecology 2006; 194, S3-11.

 

Lewiecki ME.  Overview of dual X-ray Absorptiometry.  UpToDate Online 14.1 Sep 13, 2005.  http://www.utdol.com/utd/content/topic.do?topicKey=minmetab/24392&type=A&selectedTitle=2~157

 

Lydick E, et al. Development and validation of a simple questionnaire to facilitate identification of women likely to have low bone density. Am J Manag Care 1998; 4:37–48.

 

National Osteoporosis Foundation.  Fast Facts.  http://www.nof.org/osteoporosis/diseasefacts.htm Last accessed Mar 2006.

 

Nelson HD, et al.  Screening for Osteoporosis in Post-menopausal Women: A Review of the Evidence for the U.S. Preventive Services Task Force.  Annals of Internal Medicine 2002 SEP 15; 137(6):  529-541.

 

Official Air Force Approved Aircrew Medications Quick Reference List.  AF/SGOP policy letter 27 Feb 2006.

 

Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement Online 2000 March 27-29; 17(1): 1-36. Available at: http://odp.od.nih.gov/consensus/cons/111/111_statement.htm.  Accessed Mar 2006.

 

Patterson CR, Mole PA, Wilson SJ.  Osteopenia Has a Differential Diagnosis.  Scottish Medical Journal 2001; 46(6):163-164.

 

Physician’s Guide to Prevention and Treatment of Osteoporosis.  National Osteoporosis Foundation 2003.

 

Pickard J.  Alendronate (Fosamax®).  Memorandum for HQ AFMSA/SGPA, From USAFSAM/FECI 2005 Sep 01.

 

Raisz LG.  Pathogenesis of Osteoporosis.  UpToDate.  Online version 14.3, June 1, 2006.  http://uptodateonline.com/utd/content/topic.do?topicKey=minmetab/18315&type=A&selectedTitle=15~157

 

Rosen HN.  Epidemiology and Causes of Osteoporosis.  UpToDate Online version 14.3, August 29, 2006.  http://www.utdol.com/utd/content/topic.do?topicKey=minmetab/15864&type=A&selectedTitle=1~157

 

Rosen HN.  Use of Biochemical Markers of Bone Turnover in Osteoporosis.  UpToDate.  Online version 14.3, February 23, 2006.  http://uptodateonline.com/utd/content/topic.do?topicKey=minmetab/17366

 

Rosen HN.  Screening for Osteoporosis.  UpToDate.  Online version 14.3, August 9, 2006.  http://uptodateonline.com/utd/content/topic.do?topicKey=minmetab/19499&type=A&selectedTitle=5~157

 

Rosen HN, Drezner MK.  Overview of the Management of Osteoporosis in Women.  UpToDate.  Online version 14.3, September 12, 2006.  http://www.utdol.com/utd/content/topic.do?topicKey=minmetab/13865&type=A&selectedTitle=4~157

 

Tannenbaum C, et al.  Yield of Laboratory Testing to Identify Secondary Contributors to Osteoporosis in Otherwise Healthy Women.  The Journal of Clinical Endocrinology & Metabolism 2002; 87(10):  4431-4437.

 

 

 

 

Prepared by Drs. Glenn Donnelly, Jeb Pickard and Karen Fox

Date: 12 Sep 09