Home Educatione-Learning Osteopenia and Osteoporosis in Lung Disease
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Osteopenia and Osteoporosis in Lung Disease

PCCSU Volume 25, Lesson 4


The American College of Chest Physicians offers this lesson as a review of a previously offered self-study program. The program provides information on pulmonary, critical care, and sleep medicine issues. CME is no longer available for the PCCSU program.


  • Update your knowledge and understanding of pulmonary medicine topics.
  • Update your knowledge and understanding of critical care medicine topics.
  • Update your knowledge and understanding of sleep medicine topics.
  • Learn clinically useful practice procedures.

CME Availability

Effective July 1, 2013, PCCSU Volume 25 is available for review purposes only.

Effective December 31, 2012, PCCSU Volume 24 is available for review purposes only.

Effective December 31, 2011, PCCU Volume 23 is available for review purposes only. CME credit for this volume is no longer being offered

Effective December 31, 2010, PCCU Volume 22 is available for review purposes only. CME credit for this volume is no longer being offered.

Accreditation Statement

The American College of Chest Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CME Statement

Credit no longer available as of July 1, 2013.

Disclosure Statement

The American College of Chest Physicians (CHEST) remains strongly committed to providing the best available evidence-based clinical information to participants of this educational activity and requires an open disclosure of any potential conflict of interest identified by our faculty members. It is not the intent of CHEST to eliminate all situations of potential conflict of interest, but rather to enable those who are working with CHEST to recognize situations that may be subject to question by others. All disclosed conflicts of interest are reviewed by the educational activity course director/chair, the Education Committee, or the Conflict of Interest Review Committee to ensure that such situations are properly evaluated and, if necessary, resolved. The CHEST educational standards pertaining to conflict of interest are intended to maintain the professional autonomy of the clinical experts inherent in promoting a balanced presentation of science. Through our review process, all CHEST CME activities are ensured of independent, objective, scientifically balanced presentations of information. Disclosure of any or no relationships will be made available for all educational activities.

CME Availability

Volume 25 Through June 30, 2013
Volume 24 Through December 31, 2012
Volume 23 Through December 31, 2011
Volume 22 Through December 31, 2010

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PCCSU Volume 25 Editorial Board

Steven A. Sahn, MD, FCCP

Director, Division of Pulmonary and Critical Care Medicine, Allergy, and Clinical Immunology
Medical University of South Carolina
Charleston, SC

Dr. Sahn has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Deputy Editor
Richard A. Matthay, MD, FCCP

Professor of Medicine
Section of Pulmonary and Critical Care Medicine
Yale University School of Medicine
New Haven, CT

Dr. Matthay has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Alejandro C. Arroliga, MD, FCCP
Professor of Medicine
Texas A&M Health Science Center
College of Medicine
Temple, TX

Dr. Arroliga has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Paul D. Blanc, MD, FCCP
Professor of Medicine
University of California, San Francisco
San Francisco, CA

Dr. Blanc has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health, Flight Attendants Medical Research Institute – university grant monies
University of California San Francisco, US Environmental Protection Agency, California Environmental Protection Agency Air Resources Board – consultant fee
Habonim-Dror Foundation Board of Trustees – fiduciary position

Guillermo A. do Pico, MD, FCCP
Professor of Medicine
University of Wisconsin Medical School
Madison, WI

Dr. do Pico has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Ware G. Kuschner, MD, FCCP
Associate Professor of Medicine
Stanford University School of Medicine
Palo Alto, CA

Dr. Kuschner has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Teofilo Lee-Chiong, MD, FCCP
Associate Professor of Medicine
National Jewish Medical Center
Denver, CO

Dr. Lee-Chiong has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health – grant monies (from sources other than industry)
Covidien, Respironics, Inc. – grant monies (from industry-related sources)
Elsevier – consultant fee

Margaret Pisani, MD, MPH, FCCP
Assistant Professor of Medicine
Yale University School of Medicine
New Haven, CT

Dr. Pisani has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Stephen I. Rennard, MD, FCCP
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

Dr. Rennard has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

AstraZeneca, Biomark, Centocor, Novartis – grant monies (from industry-related sources)

Almirall, Aradigm, AstraZeneca, Boehringer Ingelheim, Defined Health, Dey Pharma, Eaton Associates, GlaxoSmithKline, Medacrop, Mpex, Novartis, Nycomed, Otsuka, Pfizer, Pulmatrix, Theravance, United Biosource, Uptake Medical, VantagePoint – consultant fee/advisory committee

AstraZeneca, Network for Continuing Medical Education, Novartis, Pfizer, SOMA – speaker bureau

Ex Officio
Gary R. Epler, MD, FCCP

Clinical Associate Professor of Medicine
Harvard Medical School
Brigham & Women's Hospital
Boston, MA

Dr. Epler has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Lilly Rodriguez
ACCP Staff Liaison

By Marilynn Prince-Fiocco, MD, FCCP

Dr. Prince-Fiocco is Associate Professor, Texas A&M College of Medicine; Staff Physician, Division of Pulmonary/Critical Care; and Director, Cystic Fibrosis Adult Affiliate Center, Temple, TX.

Dr. Prince-Fiocco has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within this chapter.


  1. Define osteopenia and osteoporosis according to the World Health Organization classification system.
  2. Describe the association of osteopenia and osteoporosis with specific lung diseases.
  3. Discuss the role of risk factors relevant to the development of osteopenia and osteoporosis in lung disease.
  4. Recognize the association of vitamin D deficiency with various forms of lung disease.
  5. Discuss the need for long-term data addressing management of osteopenia and osteoporosis in lung disease.

Key words: asthma; bronchiectasis; COPD; cystic fibrosis; FRAX®; glucocorticoids; lung transplantation; osteopenia; osteoporosis; pulmonary transplantation; vitamin D

Abbreviations: BMD = bone mineral density; CF = cystic fibrosis; COPD = chronic obstructive pulmonary disease; DEXA = dual energy x-ray absorptiometry; FRAX® = WHO Fracture Risk Assessment tool; NHANES III = Third National Health and Nutrition Examination Survey; RANKL = receptor activator of NFκB ligand; SD = standard deviation; TORCH = Towards a Revolution in COPD Health; WHO = World Health Organization

The association of osteoporosis and chronic lung disease was recognized at least 50 years ago: “That osteoporosis may occur in chronic respiratory failure is supported by the well-known phenomenon of ‘cough’ fractures in chronic bronchitis: it is most unlikely that normal ribs could be fractured by coughing.”1 The author suggested that chronic respiratory acidosis was causative through a direct effect of low tissue pH on bone.

Osteoporosis and osteopenia have been recognized as debilitating extrapulmonary features of several forms of chronic lung disease, especially chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis (CF), as well as post-lung transplant. Various risk factors, including glucocorticoid therapy, inflammation, cigarette smoking, nutrition, vitamin D deficiency, hypoxemia, and sedentary habits have been identified. Despite some supportive epidemiologic evidence, much of the current literature is speculative, with management guidelines largely intuitive and derived from other patient populations. Attention to osteoporosis is growing, and there is a body of knowledge available. Nevertheless, there is a paucity of long-term data regarding effective management, and pulmonologists have not yet assumed a primary obligation for management of this aspect of their patients’ needs.

Osteoporosis has been defined pathologically as a systemic skeletal disease characterized by microarchitectural reduction of bone tissue leading to low bone mass and increased bone fragility, thus increasing the risk of fracture.2 Bone mineral density (BMD) measurements are used for diagnosis, based on a World Health Organization (WHO) working group analysis of lifetime fracture risk for all fractures (hip, vertebrae, forearm, humerus, and pelvis). BMD may be expressed as T scores and Z scores. The T score is a standard deviation compared with a young adult sex-matched control population, while the Z score is a standard deviation compared with an age-and sex-matched control population. The most common current means of measurement is through dual energy x-ray absorptiometry at the hip and spine, which involves very low doses of radiation.3 The WHO selected a cut point of 2.5 standard deviations (SDs) or more below the mean for healthy young adult women (T score ≤-2.5), or a history of atraumatic fracture, to characterize osteoporosis, based on increased fracture risk.4 A T score between -1.0 and -2.5 defines the separate category of osteopenia in the WHO classification, recognizing that fracture risk is a continuum rather than a threshold value5 (Table 1).

Table 1Bone Density Measurement by DEXA

Scoring System Reference Standard Normal Osteopenia Osteoporosis
T score
(SD from mean)
Young adult
female mean
Above (-1) Between (-1)
and (-2.5)
Z score
(SD from mean)
Age- and gender-
matched mean
Above (-2) Not specifically defined Not specifically defined

DEXA = dual energy x-ray absorptiometry.

It is notable that the WHO classification was initially applied to fracture risk assessment in Caucasian postmenopausal women, with the predictive applicability of these standards to other populations initially unclear. Expanded epidemiologic data are now available to establish the prevalence of low femoral neck bone mass in men and nonwhite populations, with less well established data regarding fracture risk prediction6 but providing a baseline for assessing the potential contribution of risk factors other than age in determining the likelihood of this debilitating disease state. The WHO has recently developed an easily used algorithm, the FRAX® (WHO Fracture Risk Assessment tool), which is available online as a calculator to assist clinicians with the estimation of fracture risk and subsequent decisions regarding treatment. The tool was developed from a large body of epidemiologic data on postmenopausal women and men older than 50 years, and its application to younger individuals with low bone mass is not established.7,8 Risk factors incorporated in the FRAX algorithm are listed in Table 2.9

Table 2Risk Factors for FRAX

1.     Age (between 40-90 years)
2.     Sex
3.     Weight (kg)
4.     Height (cm)
5.     Previous fracture
6.     Parent fractured hip
7.     Current smoking
8.     Glucocorticoids
9.     Rheumatoid arthritis
10.   Secondary osteoporosis
11.   Alcohol (3 or more units per day)
12.   Femoral neck BMD (g/cm2)

BMD = bone mineral density; FRAX = WHO Fracture Risk Assessment tool.

The FRAX algorithm includes two major risk factors frequently encountered in patients with lung disease: glucocorticoid use and current smoking. However, there are significant limitations in its use for pulmonary patients. Previous smoking history is not specifically included. The list of factors identified as causes of “secondary osteoporosis” does not specifically include any form of lung disease—although chronic malnutrition/malabsorption are included, and these are common features of advanced pulmonary disease. If pulmonary disease has independent effects on bone mass or architecture, then FRAX may underestimate the risk of fracture in the assessment of chronic pulmonary patients. It is important to recognize that vitamin D status is not included in the FRAX model.

In the nonpulmonary literature, a recent comprehensive review of factors involved in secondary osteoporosis does not recognize pulmonary diseases as predisposing conditions, except for CF and patients who undergo lung transplant.10 Similarly, the most recent update from the US Preventive Services Task Force regarding screening for osteoporosis does not delineate pulmonary disease as a specific risk factor.11 However, four forms of chronic pulmonary disease have been clearly associated with an increased prevalence of osteoporosis: COPD, asthma, CF, and lung transplant. There are less data available for other processes, including non-CF related bronchiectasis and interstitial fibrosis.


Of the pulmonary processes associated with osteoporosis, COPD is the most common in the adult population. Cross-sectional prevalence studies12,13,14 have demonstrated an increasing risk of osteoporosis in patients with COPD with more advanced disease. A representative study13 compared BMD in patients with COPD in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages II-IV, reporting osteopenia in 29% of patients in stage II, 40% in stage III, and 57% in stage IV. Osteoporosis occurred in 9.6% in stage III and 18% in stage IV. There is a wealth of literature regarding glucocorticoid use and osteoporosis in nonpulmonary disease that can be appropriately extrapolated to pulmonary patients. Our attention to that factor in caring for our patients would be a sufficient reason to call attention to the process. Many of our patients do not receive steroids on a chronic basis; however, and any given patient often receives steroid prescriptions from multiple providers throughout the years, with no specific cumulative value established to direct therapy. Furthermore, the prevalence of vertebral fractures is high in patients with COPD who have not received glucocorticoids.3,15

Consideration of inhaled glucocorticoid use is often alluded to, but has rarely been systematically studied in the COPD population, with greater attention previously given to the use of inhaled steroids in pediatric patients with asthma. However, a recent subset of patients included in the TORCH (Toward a Revolution in COPD Health) study was analyzed with exactly that purpose, with the conclusion that osteopenia and osteoporosis are highly prevalent in patients with COPD, irrespective of gender, but that no significant effect on BMD was detected for inhaled corticosteroid therapy compared with placebo. At baseline, the overall prevalence of osteopenia and osteoporosis was 65%. Osteopenia prevalence was equal in men and women (approximately 42%), while 30% of women and 18% of men had osteoporosis. Prior to the study, the prevalence of identification and treatment of osteoporosis was quite low, especially in men.16

It is the more recent recognition of COPD as a systemic inflammatory disease that adds impact to our study of the process. Osteoporosis is the result of an unhealthy balance of osteoblastic and osteoclastic factors, and increased bony destruction or bone turnover with ineffective bone synthesis will lead to osteoporosis. The interactions are complex, and the role of cytokine stimulation of bone resorption is controversial.3 T cells may express the receptor activator of NFκB ligand (RANKL), binding to the RANK receptor on preosteoclasts to initiate osteoclastogenesis. T cells may also produce tumor necrosis factor (TNF), which could augment RANKL-induced osteoclastogenesis.17

Multiple chemoattractants and inflammatory markers have been recognized in COPD. These include interleukin (IL)-6, TNF-α receptors, members of the matrix metalloproteinase enzyme family, acute phase proteins such as C-reactive protein and fibrinogen, and markers of oxidant stress such as hydrogen peroxide and nitric oxide.13,18 The presence of these biomarkers has been associated with more severe lung disease, although causal aspects have not been determined. These biomarkers have been related to other aspects of inflammatory comorbidities. For example, IL-6 has been implicated as a factor in atherosclerotic disease, with increased cardiovascular risk in patients with COPD; IL-6 is also involved in regulation of bone turnover and osteoporosis development.13 TNF-α has been recognized as a stimulator of osteoclastic bone resorption, which is involved in postmenopausal osteoporosis.

In addition to glucocorticoid use, patients with COPD express several potential risk factors that undoubtably contribute to the prevalence of osteoporosis. Postmenopausal women are increasingly represented in this population, so primary osteoporosis, linked to age and estrogen decline, are factors in that group. Known secondary risk factors include tobacco use. Smoking exerts a toxic effect on osteoblast function, with additional contributions of acceleration of menopause and accelerated degradation of estrogens. Hip fracture risk among smokers is greater than in nonsmoking subjects in all groups but rises with age and declines with quitting.3 Alcohol use is independently associated with osteoporosis in a dose-dependent fashion, and the combination of smoking and alcohol use presents a high risk of fracture.15

Immobilization is associated with bone loss, while weight-bearing and resistance exercise are associated with increased bone mass. Patients with advanced COPD, as well as pulmonary patients with other advanced diseases, are often quite sedentary. There is little evidence that specific pulmonary rehabilitation programs can reverse this dramatic level of inactivity. However, exercise programs may diminish the risk of fracture by decreasing the risk of falls.3,17

The relative prevalence of vitamin D deficiency in the general COPD population, in comparison with the general population, may be increased. More significantly, there is an association between low FEV1 levels and vitamin D levels in patients with COPD.19 Causality has not been established, as vitamin D deficiency may serve as a marker for the inflammatory state, as well as a representation of other potential nutritional deficiencies that may influence tissue integrity and pulmonary function.

Indeed, malnutrition in COPD must be assessed as a risk factor for osteoporosis. Low BMD has been associated with low BMI in otherwise healthy subjects. This correlation between BMD and BMI may be expressed in patients with end-stage COPD who lose weight as the disease progresses due to decreased intake and increased energy requirements.15

Despite early speculation regarding the role of respiratory acidosis and hypoxemia in the development of osteoporosis,1 there is little information to specifically separate patients with hypoxemia with COPD from others in respect to risks of osteoporosis and fractures.

The presence of pain and increased sedentary status following fractures in patients with COPD imposes a vicious spiral of general declining function, with increased mortality as well as increased dependence on caretakers. In addition, specific physiologic factors related to thoracic vertebral fractures produce a decline in pulmonary function. Progressive kyphosis due to thoracic vertebral fractures may decrease lung volume, causing a restrictive ventilatory defect, impairment of respiratory muscle function, and decrease in vital capacity, total lung capacity, and inspiratory capacity.3,15,18,20


Patients with severe, corticosteroid dependent asthma in adulthood may share the sedentary lifestyle of patients with advanced COPD. The role of corticosteroids in affecting bone mass has been addressed with regard to both inhaled and oral corticosteroids.21 However, low bone mass has three major pathogenetic causes: failure to achieve optimal peak bone mass, increased bone resorption, and inadequate bone formation. Severe asthma often begins in childhood, so the first problem—inadequate achievement of optimal peak bone mass—is of more concern in the population of child and adolescent patients receiving glucocorticoids than in patients with COPD. Accelerated bone loss has been observed even in patients on low-dose oral steroids or on inhaled steroids despite the lack of demonstrable disturbance of the hypothalamic- pituitary-adrenal axis, although the actual development of osteoporosis has not been observed.21 Chronic inhaled steroid use remains a guideline therapy for persistent asthma. At this point, there is little evidence of other specific effects of asthma on the development of osteoporosis, except for the shared secondary risk factors, such as immobility, smoking, and poor nutritional status identified in patients with COPD.


CF is unique in its expression of bone mineralization disorders in pulmonary disease. More than 40% of patients with CF are now older than 18 years, and bone fractures impose additional disability and suffering, demanding attention to early recognition and treatment.22 An understanding of osteoporosis and osteopenia in CF is an example of the need for multidisciplinary, comprehensive care of these patients, involving gastroenterologists and endocrinologists in concert with the pulmonologists who have been their primary caretakers. The combination of inflammatory factors, chronic infection, malabsorption and maldigestion, low-BMI, specific vitamin D deficiency, physical inactivity, delayed pubertal maturation, and variable glucocorticoid use combine to form the perfect storm.23 The causal predominance of these various factors is incompletely understood. The CF transmembrane conductance regulator gene (CFTR) is expressed in multiple epithelial organs, including the lungs, but it does not appear to specifically affect the bones. Now that more than 40% of patients with CF are adults, there is an increasing need for attention to this aspect of their disease because fractures impose additional disability and suffering and may present an obstacle to lung transplantation.22 Prevalence studies indicate a severe problem, recognizing that these are primarily young adults. Cross-sectional surveys of adults indicate that 20% to 34% has Z scores below -2.0, and 10% has T scores less than -2.5,22 scores associated with a significant increase in fracture risk.

Bone demineralization in CF may emerge in childhood, with several small prevalence studies indicating lower Z scores in children with CF, as well as correlation of BMD values with disease severity.24 BMD has been associated with age, weight, and BMI. Puberty is a critical period for bone growth and mineralization, and patients with CF often exhibit delayed puberty and reduced pubertal growth. The prevalence increases with age, and the majority of adult patients with CF exhibit at least osteopenia.22 In a primary study,23 there was a clear association with vitamin D levels, while the association with steroid use did not reach statistical significance. Adequate vitamin D levels are difficult to achieve in CF, frequently requiring high-dose supplementation to achieve and maintain adequate levels, presumably due to difficulty in absorption of this fat-soluble vitamin in patients with pancreatic insufficiency. Current recommendations indicate that screening with dual energy x-ray absorptiometry scans is appropriate at an early age, at or prior to puberty.24 Adequate vitamin D is deemed essential for bone growth, and continued attention to this parameter is a standard of care for patients with CF. Calcium supplementation and vitamin K supplementation are recommended. Sex hormone replacement therapy is a consideration on an individual basis. Antiresorptive therapy in the form of bisphosphonates is the best-studied treatment in small studies and has shown efficacy. However, the optimal agents, route of delivery, and age to initiate treatment are unclear.22

A few small studies25 have addressed the question of the risk of osteopenia and osteoporosis in non-CF bronchiectasis, but there is no comprehensive evaluation of this association. Certainly, some other forms of non-CF bronchiectasis share similar aspects of chronic inflammation and infection, such as other ciliary dyskinesias. In addition, there appears to be a phenotypic similarity between elderly Caucasian female patients with bronchiectasis and those who fall into the risk category for postmenopausal osteoporosis, with vitamin D status as one aspect worth further study.

Lung Transplantation

Osteopenia and osteoporosis are major concerns in both pretransplant and posttransplant pulmonary patients. Patients referred for lung transplantation represent an advanced level of disease, and there is a high prevalence of pretransplant osteoporosis and atraumatic fractures in all diagnostic categories.26,27 A representative study26 indicated a pretransplant finding of Z scores at or below the fracture threshold in 75% of patients with CF, 45% of patients with COPD, and 15% of patients with other pulmonary diseases. Previously noted risk factors, such as sedentary status and glucocorticoid use apply, and these patients are commonly profoundly dyspneic, hypoxemic, and cachectic. Low BMD has been correlated with low BMI in some studies. In the first few years following transplant surgery, a 5% to 10% additional loss of BMD has been described.26,27 Fracture risk is higher in pulmonary patients than in other transplant categories, although all organ transplant patients have an increased risk of fracture. A sobering high fracture rate of 225 fractures per 1,000 person-years post-lung transplant has been recorded.26 This increased risk of fracture in the pulmonary group reflects their lower BMI pretransplant compared to other organ recipients, such as patients with renal failure, who often do not suffer from the same degree of disability. Therefore, despite similar posttransplant bone loss, their lower starting-point BMD further increases their risk of fracture at more severe levels of demineralization. Therefore, while other quality-of-life measures improve, the fracture rate increases, and in posttransplant patients, has been reported at 225 per 1,000 person-years.26 Vitamin D supplementation and calcium supplementation have not improved the short-term risk. Posttransplant immunosuppressive medications have been presumed to be major factors regarding bone mineral loss. Little has been said regarding the role of increased mobility itself in raising the risk of falls and fracture, recognizing that atraumatic fracture is generally defined as one that occurs with a fall from a person’s own height or less. The need for immunosuppressive agents will continue, so the challenges in this area include the earlier recognition and treatment of pretransplant osteoporosis, as well as the most effective forms of pharmacologic and rehabilitation management posttransplant.

Vitamin D

Vitamin D recently has received enormous attention, and a role is recognized for this fat-soluble vitamin in multiple aspects of health and disease. The prevalence of vitamin D deficiency worldwide appears to be increasing. Absorbed from skin and dietary sources as vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol), this fat-soluble prohormone is converted first by the liver to 25-OH vitamin D and then by the kidney to the active form, calcitriol, 1,25-OH vitamin D. This vitamin is essential in calcium homeostasis, regulating calcium and phosphorus absorption from the intestine and affecting osteoblast and osteoclast function. Therefore, adequacy of vitamin D is a well-recognized factor in osteoporosis and osteopenia of all causes. However, vitamin D has additional functions in cellular differentiation, muscle cell growth and function, inhibition of angiogenesis, neuroprotection, fibroblast proliferation, collagen synthesis, and the formation of matrix metalloproteinases, all of which have potential implications for physiologic processes involved in lung disease.20,29 The Third National Health and Nutrition Examination Survey (NHANES III) identified a strong relationship between lower serum concentrations of 25-OH vitamin D and FEV1 and FVC, independent of multiple factors, including BMI and smoking history.20 Attention to vitamin D levels in pulmonary patients identified as having osteoporosis may have positive effects on other poorly understood factors affecting pulmonary structure and function. There has been no demonstration that vitamin D supplementation provides such benefit, but prospective, prolonged study in this area is worthwhile.


There are no specific guidelines for screening, assessment, or pharmacologic management of osteopenia and osteoporosis in lung disease. General recommendations were primarily formulated to address postmenopausal osteoporosis in otherwise healthy individuals. There must be careful, individual attention to minimizing secondary factors such as glucocorticoid use, smoking, and sedentary status. Screening patients with early diagnoses of lung disease, despite age or other risk factors, would establish a baseline and help to determine potential primary biologic effects of pulmonary disease processes.

The goal of osteoporosis treatment is to prevent fractures. Although the dual energy x-ray absorptiometry (DEXA) as a measure of bone density is the primary screening tool, the microarchitecture of the bone is also important in determining bone fragility. However, microarchitecture is difficult to evaluate, with bone biopsy required for definitive assessment. Bone turnover markers are a potential tool, but difficult to interpret due to substantial day-to-day variability, representation of the entire skeleton, and lack of enough information currently to guide individual therapy.30

Available treatments include primarily antiresorptive and anabolic medications. All currently indicated osteoporosis therapies have antifracture efficacy at the spine, and some decrease fracture at nonvertebral sites, including the hip. Bisphosphonates are the current first-line therapy, with more effect in decreasing bone turnover than available selective estrogen receptor modulators.30 Newer selective estrogen receptor agents may be more effective. Parathyroid hormone and teriparatide are anabolic agents that improve both bone mineral density and microarchitecture, with acceleration of new bone formation. Denosumab is a novel agent recently approved for the treatment of osteoporosis in postmenopausal women. This human monoclonal antibody binds to RANKL, inhibiting the RANK/RANKL interaction that promotes osteoclast activity, thus modulating bone turnover.30 Comparative studies of different agents in pulmonary patients have not been described.

Calcium and vitamin D supplementation is a basic component of the management of demineralization. However, recommended doses for supplementation were based on maintenance of skeletal health, rather than rebuilding. The optimal 25-OH vitamin D target level also is not well known. While 30 nmol/L is generally considered adequate, some sources feel that much higher levels are optimal. Based on measurement of parathyroid hormone levels, a serum biomarker that rises as serum 25-OH vitamin D levels fall, a recent recommendation suggests 80 nmol/L to be a reasonable target level because parathyroid hormone levels tend to level off at that point.31 Current recommendations for vitamin D supplementation may be inadequate, although the cutaneous absorption of vitamin D through sunlight imposes substantial individual variability in intake unrelated to diet and supplements. In the setting of CF and other diseases leading to malabsorption, much higher supplemental doses will be required.23

Postmenopausal treatment guidelines for medications, dosing, and initiation of therapy should generally apply in the absence of specific studies indicating a reason to alter those recommendations. Adequate calcium and vitamin D supplementation, as well as weight-bearing exercise, are adjunctive to pharmacologic therapy. Use of pharmacologic therapy in addition to calcium and vitamin D therapy does not require a bone density in the osteoporotic range. The National Osteoporosis Foundation suggests consideration of pharmacologic treatment in addition to calcium and vitamin D supplementation when the T score falls below -1.5 in the presence of one or more risk factors, or when the T score is below -2.0 without specific risk factors.32 A summary of generally available US Food and Drug Administration-approved medications and common dosing is included in Table 3.32

Table 3US Food and Drug Administration-Approved Drugs for Treatment or Prevention of Postmenopausal Osteoporosis

Drug Class Medication Route Dose
Bisphosphonates Alendronate Oral 35-70 mg weekly,
5-10 mg daily
  Risedronate Oral 35 mg weekly
  Ibandronate Oral
150 mg monthly,
3 mg IV quarterly
  Zoledronic acid IV 5 mg yearly
Selective estrogen receptor modulator Raloxifene Oral 60 mg daily
Anabolic agents Teriparatide
(Recombinant human parathyroid hormone)
Subcutaneous 20 µg daily
Estrogens Various Oral, transdermal Various



Recognition of the role that osteoporosis and osteopenia play in the cumulative disability of the advanced pulmonary patient provides an abundance of research opportunities. Long-term prospective data addressing the appearance, progression, and responsiveness to therapy is lacking in this unique subset of patients with osteoporosis. Possibilities of degenerative and regenerative processes affecting bone and lung can be explored. The specific effects of hypoxemia, kyphosis, malnutrition, and chronic inflammation must be added to traditionally recognized factors such as tobacco use, sedentary status, and glucocorticoid use to achieve a more comprehensive understanding. The benefit of early screening has not been established, and the comparative efficacy of therapeutic options has not been determined. Significant attention to skeletal health in our patients has been left to primary care physicians and other subspecialists, but this is an area where pulmonologists can take the lead. To achieve optimal comprehensive care of our patients, pulmonologists must assume a primary role in screening, assessment, and management.


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