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Lymphangioleiomyomatosis (LAM) is the result of disorderly smooth muscle proliferation throughout the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways (leading to pulmonary cyst formation and pneumothorax) and lymphatics (leading to chylous pleural effusion). LAM occurs in a sporadic form, which only affects females, who are usually of childbearing age. LAM also occurs in patients who have tuberous sclerosis. more...

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The cause of the sporadic form of LAM is unknown. This type only affects women.

The proliferating smooth muscle that occurs the type of LAM seen in patients with tuberous sclerosis (TSC-LAM) has been shown to represent clones of the smooth muscle in those patients' renal angiomyolipomas, and thus is believed to represent metastases of this "benign" tumor. There is a female properandence to TSC-LAM. (reference: Henske EP. Metastasis of benign tumor cells in tuberous sclerosis complex. Genes, Chromosomes & Cancer. Dec. 2003. 38(4):376-81)


With LAM, there is diffuse replacement of the pulmonary parenchyma by thin-walled cysts measuring 2-20 mm in diameter, with equal involvement of upper and lower lung zones. On chest X-rays, superimposition of the cysts gives a reticulonodular pattern of interstitial lung disease. High-resolution CT of the chest is both more specific for the diagnosis, as well as better able to assess the degree of pulmonary involvement.


Without lung transplant, there is a 50-80% 5-year survival rate.


  • Worsening pulmonary insuffiency
  • Pneumothorax, secondary to rupture of a cyst into the pleural space
  • Chylous pleural effusions


The association of LAM with women of childbearing age suggests that hormonal stimulation plays a role in the disease process, and several approaches to treatment involve diminishing the effect of estrogen. At one time or another, therapeutic approaches have included

  • progesterone
  • oophorectomy
  • tamoxifen
  • gonadotropin-releasing hormone (GnRH) agnonists
  • androgen therapy

No therapy is clearly efficacious, and all have undesirable side-effects.

When pulmonary function deteriorates to the point where oxygenation is inadequate, lung transplantation is usually performed. Following lung transplant (usually unilateral), LAM patients have survival curves similar to other lung transplant patients.


The drug Sirolimus (also known as Rapamycin) is being investigated in clinical trials as a possible treatment. It has been shown to shrink angiomyolipomas in animals. For more information see this interview.


LAM Action (UK)

The LAM Foundation (US)


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Bone Mineral Density in Lymphangioleiomyomatosis
From American Journal of Respiratory and Critical Care Medicine, 1/1/05 by Taveira-DaSilva, Angelo M

Estrogen deficiency and pulmonary diseases are associated with bone mineral density (BMD) loss. Lymphangioleiomyomatosis (LAM), a disorder affecting women that is characterized by cystic lung lesions, is frequently treated with antiestrogen therapy, i.e., progesterone and/or oophorectomy. Therefore, we evaluated BMD yearly in 211 LAM patients to determine the prevalence of BMD abnormalities, whether antiestrogen therapy decreased BMD, and if treatment with bisphosphonates prevented bone loss. Abnormal BMD was found in 70% of the patients and correlated with severity of lung disease and age. Greater severity of lung disease, menopause, and oophorectomy were associated with greater decline in BMD. After adjusting for differences in initial lung function and BMD, we found similar rates of BMD decline in progesterone-treated (n = 122) and untreated patients (n = 89). After similar adjustments, we found that bisphosphonate-treated patients (n = 98) had lower rates of decline in lumbar spine BMD (-0.004 ± 0.003 vs. -0.015 ± 0.003 gm/cm^sup 2^, p = 0.036) and T-scores (-0.050 ± 0.041 vs. 0.191 ± 0.041, p

Keywords: bisphosphonates; bone mineral density; interstitial lung disease; lung function; progesterone

Lymphangioleiomyomatosis (LAM), a disease affecting primarily women, is characterized by cystic lung lesions, recurrent pneumothorax, chylous effusions, lymphatic abnormalities, and abdominal tumors, i.e., angiomyolipomas and lymphangioleiomyomas (1-4). LAM occurs sporadically in patients with no evidence of genetic disease and in about one-third of women with tuberous sclerosis complex (5-7). Generally, the pulmonary manifestations dominate the clinical features of LAM. The severity of lung disease, as measured by oxygen requirements, roentgenographic abnormalities, and exercise tolerance, correlates with the severity of the lung function abnormalities (8, 9). These abnormalities, characterized by airflow obstruction and decreased diffusion capacity of the lung for carbon monoxide (DL^sub CO^), may cause respiratory failure, requiring oxygen therapy, and may result in lung transplantation or death. The rate of progression of disease, however, is variable, and some patients have a chronic course lasting more than 20 years (8, 9).

There is evidence suggesting that LAM may be influenced by hormonal factors. Indeed, not only does LAM affect primarily women (1-4), but the disease appears to progress during pregnancy (10, 11) or after the administration of estrogens (12-14). In addition, there is evidence for the colocalization of estrogen and progesterone receptors in LAM cells (15-18). Consequently, hormonal manipulations that reduce the production of estrogens, such as treatment with progesterone and/or oophorectomy, have been employed in the treatment of LAM. Because estrogen deficiency is a recognized cause of osteoporosis (19), we hypothesized that antiestrogen therapy in the presence of lung disease could adversely affect bone mineral density (BMD) in patients with LAM. To test this hypothesis, we measured BMD yearly in a large group of women with LAM followed for more than 3 years. The aims of our study were threefold: (1) to determine the prevalence and factors associated with BMD abnormalities; (2) to determine whether treatment with progesterone is associated with an accelerated loss of bone; and (3) to determine whether treatment with bisphosphonates is associated with lower rates of decline in bone density.

Some of the results of this study have been previously reported in the form of an abstract (20).


Study Population

The study population consisted of 305 patients with LAM referred to the National Institutes of Health since 1995 for participation in a natural history longitudinal study (NHLBI Protocol 95-H-0186) approved by the Institutional Review Board of the NHLBI. In addition to self-referral or referral through individual physicians, subjects were informed of the study by the LAM Foundation and the Tuberous Sclerosis Alliance. All subjects gave informed consent before enrollment. Sixty-three patients who had only one set of BMD studies and 31 patients who had lung transplantation were excluded. Complete data for analysis were available from 211 patients. The diagnosis of LAM was made by lung or intraabdominal tissue biopsy, or by clinical and roentgenographic data (9). Patients were considered to have reached menopause when menopause had occurred naturally (low estradiol levels and elevated follicle-stimulating hormone levels) or was surgically induced (bilateral oophorectomy). A patient was defined as postmenopausal if hormonal levels as well as history were consistent with a menopausal state for most of the duration of the study. The decision to initiate progesterone therapy and the choice of route of administration were made independently by the patients' physicians and were not part of the NHLBI protocol. The majority of the progesterone-treated patients were on this therapy for the duration of the study. Patients with osteoporosis were advised to take bisphosphonates but the final decision for implementation of this therapy was left up to the patient and her family physician. However, in the majority of the patients, bisphosphonate therapy was started after the first abnormal BMD test and continued thereafter. Hormonal replacement therapy was discontinued after the first visit. Compliance with progesterone or bisphosphonate therapy was monitored by interviewing the patient at the time of each visit.

BMD Measurements

BMD of the lumbar spine (anterior and lateral), proximal right femur, and right radius was assessed by dual energy X-ray absortiometry (Hologic QDR-4000, Bedford, MA). Four different values (anteroposterior and lateral lumbar spine, proximal femur and lower radius) were obtained. T-score was defined as the number of SD units below peak bone mass. Z-score was derived from age-matched reference values. BMD was classified according to World Health Organization guidelines (21): normal BMD, T-score greater than -1 SD; osteopenia, between -1 SD and -2.5 SD inclusive; and osteoporosis, T-score less than -2.5 SD.

Pulmonary Function Tests

Lung volumes, flow rates, and DL^sub CO^ were measured using a computerized system (Master Screen PFT; Erich Jaeger, Wuerzburg, Germany) according to American Thoracic Society standards (22-24).

Cardiopulmonary Exercise Testing

Patients were exercised on a bicycle ergometer or treadmill using a computerized metabolic cart (Vmax 229 Cardiopulmonary Exercise System; Sensormedics, Yorba Linda, CA), using standard incremental protocols (9). VO^sub 2^max was defined as the highest oxygen uptake observed during any 30-second measurement period.

Statistical Methods

To identify factors associated with BMD at the time of initial testing, we ran univariate regression analyses between BMD or T-scores, and age, body mass index (BMI), pulmonary function (DL^sub CO^ and FEV^sub 1^), VO^sub 2^max, menopausal state and oophorectomy. Then, using a stepwise procedure, we ran a multiple regression analysis with BMD or T-scores as the dependent variables and all the independent variables found to be statistically significant at a 0.10 level in the univariate regression analysis. The level of significance for inclusion in the model is set at p

Because our data set contained multiple BMD measurements for the 211 patients, we summarized the information from each subject by using the yearly rate of change (slope) calculated from a linear regression with the raw BMD or T-scores for each of the bone areas as the response variables and the time of each test as the independent variable, considering the first test as Time 0. The effect of bisphosphonate and progesterone treatment on the yearly rate of change in BMD was tested using a two-sided t test. Similar to the baseline analyses, we ran univariate and multivariate regression analyses to identify factors related to the rate of change in BMD. In addition to the explanatory variables considered in the baseline analyses, we included treatment or no treatment with bisphosphonatcs and progesterone, initial DL^sub CO^ or FEV^sub 1^, rate of decline in DL^sub CO^ and FEV^sub 1^, and time under observation. All data are presented as mean ± SEM. All reported p values are two-sided.


Study Population

Two hundred eleven patients are the subject of the current report. Forty of the 211 patients had tuberous sclerosis complex based on established criteria (e.g., presence of skin lesions, cerebral tubers, and a history of seizures). The diagnosis of LAM had been established 2.8 ± 0.2 years before enrollment in our study. However, based on the history of LAM-related symptoms (e.g., pneumothorax, chylous effusions, hemoptysis, breathlessness, or angiomyolipoma-related hemorrhage), it was estimated that, at the lime of the first visit, the mean duration of LAM had been 6.8 ± 0.4 years. One hundred eight patients were premenopausal and 103 were postmenopausal, of whom 43 had undergone oophorectomy. The average number of visits per patient was 3.7 ± 0.1 (range = 2-8). The mean follow-up in years was 3.2 ± 0.1 (range = 0.8-6.8) for a total of 667 patient/years. Ninety-four patients were excluded from the study. Of these, 31 patients underwent lung transplantation. Twelve patients had lung transplantation before their first visit and 19 had it subsequent to the first visit. Eight of the patients who had lung transplantation did not have BMD studies. Sixty-three patients had undergone only one BMD test before the closure of our study.

Table 1 shows baseline characteristics, including initial BMD and lung function, for the 211 patients who are the subject of our study, and the 74 patients with BMD measurements who were excluded because they had only one BMD test, of whom 11 underwent lung transplantation before having a second BMD test.

As shown in Table 1, the percentage of patients who had reached menopause or were treated with progesterone and bisphosphonates was significantly lower in the 74 excluded patients. Further, their BMI and femoral BMD were also significantly lower. Lung function, i.e., FEV^sub 1^ and DL^sub CO^, was more severely impaired in the patients who were excluded from the analyses because this group included 11 patients with very severe disease who thereafter underwent lung transplantation.

Initial BMD, Lung Function, and Maximal Oxygen Uptake

Tables 1 and 2 show initial BMD, pulmonary function, and V^sub O2^ data for the 211 patients who are the subject of this report. The overall initial frequency of osteoporosis and osteopenia by World Health Organization criteria at any of the four sites was 23% (n = 49) and 47% (n = 100), respectively. At the lumbar spine, osteopenia and osteoporosis were found, respectively, in 38% and 18% of the patients. At the proximal femur, the corresponding figures were 40% and 4%, respectively. At the anterior radius, osteopenia was observed in 18% of the patients. One patient had osteoporosis at this site. The overall frequency of osteoporosis and osteopenia in the 74 excluded patients at any of the four sites was 12% (n = 9) and 42% (n = 31), respectively.

Predictors of Initial BMD

Single regression analysis showed that bone density was positively correlated with lung function and negatively correlated with age. BMI was also a significant positive predictor of BMD but only at the femoral bone site (p

Multivariate analysis confirmed that DL^sub CO^ and BMI (femoral bone only) were positively correlated with bone density, whereas age was a negative predictor of bone density.

Predictors of Decline in BMD

Higher initial DL^sub CO^ and longer follow-up time were significantly correlated with lower rates of decline in bone density (p

A weighted multivariate analysis of the slopes of BMD and T-scores showed that menopause was associated with a greater rate of bone loss at the lumbar spine (p

Four of the 211 patients suffered fractures throughout the span of the study.

Effect of Treatment with Progesterone on BMD

One hundred and twenty-two (mean age 43.1 ± 0.8 years) of the 211 patients were treated with progesterone and 89 (mean age 45.0 ± 0.9 years) received no hormonal therapy. The average monthly dose of progesterone in the treated group was 588 ± 40 mg, and the mean duration of therapy was 62 ± 4 months. Fifty-nine of the progesterone-treated patients (48%) had reached menopause, of whom 30 (25%) had undergone oophorectomy. Forty-four (49%) of the 89 untreated patients had also reached menopause, of whom 13 (15%) had oophorectomy. A significant greater percentage of progesterone-treated patients received treatment with bisphosphonates (57 vs. 31%, p

Effect of Treatment with Biphosphonates on BMD

Ninety-eight of the 211 patients were treated with bisphosphonates and 113 received no therapy. A significantly greater percentage of patients had reached menopause in the bisphosphonate-treated group (60 vs. 39%, p

A weighted multivariate analysis of the slopes of BMD and T-scores showed that treatment with bisphosphonates was associated with a lower rate of decline in both BMD (p = 0.036) and T-scores (p

To determine whether the beneficial effect of treatment with bisphosphonates in preventing loss of bone in the lumbar spine was present in premenopausal patients, we also analyzed the data for the premenopausal subgroup only. Thirty-nine premenopausal patients were treated with bisphosphonates and 69 did not receive treatment. The conclusions remain the same in terms of the BMD variables. Furthermore, age and lung function variables are similar in both groups, which make the conclusions even stronger. We, therefore, believe that our conclusions are valid for the whole population of LAM patients and not just for the postmenopausal group.

Effect of Lung Transplantation on BMD

In 11 of the 31 patients who had lung transplantation, BMD was evaluated before transplantation and at the first posttransplantation visit. As shown in Figure 2, anterior and lateral lumbar spine T-scores declined from -0.515 ± 0.404 to -1.089 ± 0.418 (p = 0.010) and from -0.869 ± 0.587 to -2.134 ± 0.434 (p = 0.011), respectively. Femoral neck T-scores declined from -0.970 ± 0.400 to -1.220 ± 0.284 but the difference was not significant (p = 0.305). Anterior radius T-scores declined from +0.780 ± 0.395 to +0.475 ± 0.396 (p = 0.046).


Our study shows that BMD is decreased in the majority of patients with LAM, with less than one-third of the 211 patients having normal BMD. This high frequency of abnormal BMD was not related to weight loss because BMI was increased in our patients (26.9 ± 0.5 kg/m^sup 2^, range 17-53). The major factors associated with abnormal BMD appeared to be estrogen deficiency, caused by natural or surgically induced menopause, and the severity of lung disease, evidenced by a decline in DL^sub CO^ and FEV^sub 1^. Treatment with progesterone was not associated with an adverse effect on BMD. Treatment with bisphosphonates, however, was associated with a beneficial effect on lumbar spine BMD in both pre- and postmenopausal patients. Finally, lung transplantation was associated with increased loss of bone.

The prevalence of bone mineral loss in our patients was higher than that reported in women of similar age. Between the ages of 30 and 49, the proportion of white women with osteoporosis at any bone site is low (25). Above the age of fifty the frequency of osteoporosis and osteopenia increases rapidly, reaching 20% and 50%, respectively (26, 27). However, 75% of our patients were under the age of fifty, so age alone does not account for the high prevalence of abnormal BMD observed in our cohort. Furthermore, low BMD (T-score

Our patients differ considerably from those with CF or chronic obstructive pulmonary disease. Low BMI was not a factor, and there was no evidence of chronic recurrent pulmonary infections. Calcium/phosphate and vitamin D levels were, in general, within normal limits, and the majority of the patients were taking mineral and vitamin supplements, including calcium and vitamin D. Only six patients gave a history of sporadic use of oral corticosteroids, and less than one-third of the patients reported using inhaled steroids. Nevertheless, inhaled corticosteroids could possibly be an additional factor in causing bone loss in our patients. Although data on this subject are conflicting, it is believed that the duration of therapy and the dosage level are the primary factors determining whether bone loss is associated with the use of inhaled steroids (41). In our patient population, however, high-dose inhaled corticosteroids were not employed and the duration of therapy was on average less than 3 years.

The unique features of our cohort were an early onset of menopause induced by oophorectomy and treatment with progesterone. Hypoestrogenic states are major determinants of bone mass and risk of fractures in women (19, 41), whereas hormonal replacement therapy improves BMD and reduces the risk of fractures in postmenopausal women (42). Because of the potential adverse effects of estrogens on LAM (12-14), none of our postmenopausal patients received hormonal replacement therapy and all premenopausal patients discontinued the use of oral contraceptives once the diagnosis of LAM was established. However, 122 patients received progesterone therapy, and progesterone has been reported to cause bone loss in premenopausal women (43, 44). Young women who received contraceptive doses of medroxyprogesterone, especially those under the age of 20 who subsequently used it for over 15 years, experienced increased BMD loss (45); duration of therapy was correlated with bone loss (46). Use of contraceptive doses of progesterone (150 mg every 3 months) for periods ranging from 1-3 years was also associated with bone mineral loss (47-49), although the effect was largely reversible (49). Others have found no significant adverse effect of progesterone on BMD in premenopausal women (50-53). It is possible that the effects of progesterone are confined to younger patients or adolescents, in whom peak bone mass has not been achieved, who take the drug for many years (54, 55).

No adverse effects on BMD of high doses of medroxyprogesterone taken for approximately 5 years intramuscularly or orally were found in our patients. Instead, we found an improvement in radial bone BMD in progesterone-treated patients. This could be due to the fact that in our population progesterone therapy was initiated at an age well after BMD had reached its peak and the duration of progesterone therapy was not sufficiently long to produce significant effects on bone density. Furthermore, the majority of our patients were taking calcium and vitamin D supplements. Nevertheless, our findings are reassuring to those patients with LAM who choose to be treated with progesterone.

Treatment with bisphosphonates improved lumbar spine BMD but had no statistically significant effect on the other bone areas. A beneficial effect of bisphosphonates on BMD of patients with lung diseases is at best poorly documented, except in the setting of corticosteroid therapy (38, 40) or after lung transplantation (56, 57). One study, done in patients with CF after transplantation, showed that intravenous pamidronate was more effective than calcium and vitamin D in improving bone mineral density (57). Another study, conducted in 45 patients who underwent transplantation (56), showed fewer fractures and preservation of bone mass in patients treated with bisphosphonates, especially when treatment was begun before transplantation. These beneficial effects of bisphosphonates were recently (58) confirmed in a placebo-controlled randomized trial conducted in adult patients with CF.

From our study we conclude that there is a high prevalence of abnormal BMD in LAM. Based on our findings we recommend that patients with LAM, especially postoophorectomy patients, undergo periodic evaluation of BMD. We recommend that all three areas be tested: lumbar spine, femoral neck, and anterior radius. Indeed, the presence of osteoporosis at a bone site cannot be predicted by measurements at another site (21) unless T-score thresholds are modified (59). Those with osteoporosis should be treated with calcium and vitamin D supplements and bisphosphonates. In view of the rapid deterioration in BMD observed in our patients after lung transplantation, early initiation of aggressive therapy in LAM patients with severe lung disease and osteopenia at any bone site is recommended. We propose this aggressive approach because achieving a substantial reduction of osteoporotic fractures, which may adversely affect lung function (40), cannot probably be accomplished by treating only patients with T-scores of -2.5 or less (60). Moreover, patients undergoing eventual lung transplantation will be exposed to medications that lead to further loss of bone. In addition to pharmacologic therapy, weight-bearing exercise and strength training should be encouraged (59) because of the growing evidence that exercise improves bone density (61, 62).


1. Kitaichi M, Nishimura K, Harumi I, Izumi T. Pulmonary lymphangioleiomyomatosis: a report of 46 patients including a clinicopathologic study of prognostic factors. Am J Respir Crit Care Med 1995;151:527-533.

2. Sullivan EJ. Lymphangioleiomyomatosis: a review. Chest 1998;114:1689-1703.

3. Chu SC, Horiba K, Usuki J, Avila NA, Chen CC, Travis WD, Ferrans V, Moss J. Comprehensive evaluation of 35 patients with Lymphangioleiomyomatosis. Chest 1999;115:1041-1052.

4. Urban TJ, Lazor R, Lacronique J, Murris M, Labrune S, Valeyre D, Cordier JF. Pulmonary lymphangioleiomyomatosis: a study of 69 patients. Medicine 1999;78:321-337.

5. Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc 2000;75:591-594.

6. Moss J, Avila NA, Barnes PM, Litzenberger RA, Bechtle J, Brooks P, Hedin CJ, Hunsberger S, Kristof AS. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med 2001;163:669-671.

7. Franz DN, Brody A, Meyer C, Leonard J, Chuck G, Dabora S, Sethuraman G, Colby TV, Kwiatkowski DJ, McCormack FX. Mulational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med 2001;164:661-668.

8. Taveira-DaSilva AM, Hedin CJ, Stylianou MP, Travis WD, Matsui K, Ferrans VJ, Moss J. Reversible airflow obstruction, proliferation of abnormal smooth muscle cells and impairment of gas exchange as predictors of outcome in lymphangioleiomyomatosis. Am J Respir Crit Care Med 2001;164:1072-1076.

9. Taveira-DaSilva AM, Stylianou MP, Hedin C, Kristof AS, Avila NA, Rabel A, Travis WD, Moss J. Maximal oxygen uptake and severity of disease in lymphangioleiomyomatosis. Am J Respir Crit Care Med 2003;168:1427-1431.

10. Yockey CC, Riepe RE, Ryan K. Pulmonary lymphangioleiomyomatosis complicated by pregnancy. Kans Med 1986;87:277-278.

11. Brunelli A, Catalini G, Fianchini A. Pregnancy exacerbating unsuspected mediastinal lymphangioleiomyomatosis and chylothorax. Int J Gynaecol Obstet 1996;52:289-290.

12. Shen A, Iseman MD, Waldron JA, King T. Exacerbation of pulmonary lymphangioleiomyomatosis by exogenous estrogens. Chest 1987;91:782-785.

13. Yano S. Exacerbation of pulmonary lymphangioleiomyomatosis by exogenous oestrogen used for infertility treatment. Thorax 2002;57:1085-1086.

14. Oberstein EM, Fleming LE, Gomez-Marin O, Glassberg MK. Pulmonary lymphangioleiomyomatosis (LAM): examining oral contraceptive pills and onset of disease. J Womens Health 2003;12:81-85.

15. Colley MH, Geppert E, Franklin WA. Immunohistochemical detection of steroid receptors in a case of lymphangioleiomyomatosis. Am J Surg Pathol 1989;13:803-807.

16. Berger U, Khaghani A, Pomerance A, Yacoub MH, Coombes CR. Pulmonary lymphangioleiomyomatosis and steroid receptors. Am J Clin Pathol 1990;93:609-614.

17. Ohori NP, Yousem SA, Sonmez-Alpan E, Colby TV. Estrogen and progesterone receptors in lymphangioleiomyomatosis, epithelioid hemangioendothelioma, and sclerosing hemangioma of the lung. Am J Clin Pathol 1991;96:529-535.

18. Matsui K, Takeda K, Zu-Xi Y, Valencia J, Travis WD, Moss J, Ferrans V. Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy: an immunochemical study. Am J Respir Crit Care Med 2000;161:1002-1009.

19. Richelson LS, Wahner HW, Melton LJ III, Riggs BL. Relative contributions of aging and estrogen deficiency to postmenopausal bone loss. N Engl J Med 1984;311:1273-1275.

20. Taveira-DaSilva AM, Hathaway O, Moss J. Effect of progesterone (PG) and bisphosphonates (B) on bone mineral density (BMD) in patients with lymphangioleiomyomatosis (LAM) [abstract]. Am J Respir Crit Care Med 2004;169:A225.

21. Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994;9:1137-1141.

22. American Thoracic Society. Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis 1991;144:1202-1218.

23. American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1994;152:1107-1136.

24. American Thoracic Society. Single-breath carbon monoxide diffusing capacity (transfer factor): recommendations for a standard technique-1995 update. Am J Respir Crit Care Med 1995;152:2185-2198.

25. Kanis JA, Glüer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporos Int 2000;11:192-202.

26. Looker AC, Johnston CC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Lindsay RL. Prevalence of low femoral bone density in older US women from NHANES III. J Bone Miner Res 1995;10:796-802.

27. Looker AC, Orwoll ES, Johnston CC, Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP. Prevalence of low femoral bone density in older US women from NHANES III. J Bone Miner Res 1997;11:1761-1768.

28. Lewiecki E. Low bone mineral density in premenopausal women. South Med J 2004;97:544-550.

29. Conway SP, Morton AM, Oldroyd B, Truscott JG, White H, Smith AH, Haigh I. Osteoporosis and osteopenia in adults with cystic fibrosis: prevalence and associated factors. Thorax 2000;55:798-804.

30. Ionescu AA, Nixon LS, Evans WD, Stone MD, Lewis-Jenkins V, Chatham K, Shale DJ. Bone density, body composition, and inflammatory status in cystic fibrosis. Am J Respir Crit Care Med 2000;162:789-794.

31. Gronowitz E, Garemo M, Lindblad A, Mellstrom D, Strandvik B. Decreased bone mineral density in normal-growing patients with cystic fibrosis. Acta Paediatr 2003;92:688-693.

32. Nishimura Y, Nakata H, Tsutsumi M, Maeda H, Yokoyama M. Relationship between changes of bone mineral content and twelve-minute walking distance in men with chronic obstructive pulmonary disease: a longitudinal study. Intern Med 1997;36:450-453.

33. Incalzi RA, Caradonna P, Ranieri P, Basso S, Fuso L, Pagano F, Ciappi G, Pistelli R. Correlates of osteoporosis in chronic obstructive pulmonary disease. Respir Med 2000;94:1079-1084.

34. Brousse C, Nguyen-Plantin S, Friard S, Grenet D, Stern M. Étude de la densilé minérale osseuse chez des patients insuffisants respiratoires chroniques. Rev Mal Respir 2001;18:411-415.

35. Tschopp O, Boehler A, Speich R, Weder W, Burkhardt S, Russi EW, Schmid C. Osteoporosis before lung transplantation: association with low body mass index, but not with underlying disease. Am J Transplant 2002;2:167-172.

36. Lekamwasam S, Trivedi DP, Khaw KT. An association between respiratory function and bone mineral density in women from the general community: a cross sectional study. Osteoporos Int 2002;13:710-715.

37. Sin DD, Man JP, Man SF. The risk of osteoporosis in Caucasian men arid women with obstructive lung disease. Am J Med 2003;114:10-14.

38. Biskobing DM. COPD and osteoporosis. Chest 2002;121:609-620.

39. Ionescu AA, Schoon E. Osteoporosis in chronic obstructive pulmonary diseases. Eur Respir J 2003;22:64s-75s.

40. Gluck O, Colice G. Recognizing and treating glucocorticoid-induced osteoporosis in patients with pulmonary diseases. Chest 2004;125:1859-1876.

41. Cummings SR, Kelsey JL, Nevitt MC, O'Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 1985;7:178-208.

42. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the women's health initiative randomized trial. JAMA 2003;290:1729-1738.

43. Cundy T, Evans M, Roberts H, Wattie D, Ames R, Reid IR. Bone density in women receiving depot progesterone acetate for contraception. BMJ 1991;303:13-16.

44. Mark S. Premenopausal bone loss and depot medroxyprogesterone acetate administration. Int J Gynecol Obstet 1994;47:269-272.

45. Cundy T, Cornish J, Roberts H, Elder H, Reid IR. Spinal bone density in women using depot medroxyprogesterone contraception. Obstet Gynecol 1998;92:569-573.

46. Scholes D, Lacroix AZ, Ott SM, Ichikawa LE, Barlow WE. Bone mineral density in women using depot medroxyprogesterone acetate for contraception. Obstet Gynecol 1999;93:233-238.

47. Berenson AB, Radecki CM, Grady JJ, Rickert VI, Thomas A. A prospective, controlled study of hormonal contraception on bone mineral density. Obstet Gynecol 2001;98:576-582.

48. Banks E, Berrington A, Casabonne D. Overview of the relationship between use of progestogen-only contraceptives and bone mineral density. Br J Obstet Gynaecol 2001;108:1214-1221.

49. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM. Injectable hormone contraception and bone density: results from a prospective study. Epidemiology 2002;13:581-587.

50. Globade B, Ellis S, Murby B, Randall S, Kirkman R. Bone density in long term users of depot progesterone. Br J Obstet Gynaecol 1998;105:790-794.

51. Merki-Feld GS, Neff M, Keller PJ. A prospective study on the effects of depot progesterone acetate on trabecular and cortical bone after attainment of peak bone mass. Br J Obstet Gynaecol 2000;107:863-869.

52. Tang OS, Tang G, Yip PSF, Li B. Further evaluation on long-term depot-progesterone acetate use and bone mineral density: a longitudinal cohort study. Contraception 2000;62:161-164.

53. Merki-Feld GS, Neff M, Keller PJ. A 2-year prospective study on the effects of depot progesterone acetate on bone mass-response to estrogen and calcium therapy. Contraception 2003;67:79-86.

54. Kass-Wolff JH. Bone loss in adolescents using Depo-Provera. J Soc Pediatr Nurs 2001;6:21-31.

55. Busen NH, Britt RB, Rianon N. Bone mineral density in a cohort of adolescent women using depot progesterone acetate for one to two years. J Adolesc Health 2003;32:257-259.

56. Cahill BC, O'Rourke MK, Parker S, Stringham JC, Karwande SV, Knecht TP. Prevention of bone loss and fracture after lung transplantation. Transplantation 2001;72:1251-1255.

57. Aris RM, Lester GE, Renner JB, Winders A, Blackwood AD, Lark RK, Ontjes DA. Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Resptr Crit Care Med 2000;162:941-946.

58. Aris RM, Lester GE, Renner JB, Winders A, Blackwood AD, Lark RK, Ontjes DA. Efficacy of alendronate in adults with cystic fibrosis with low bone density. Am J Respir Crit Care Med 2004;169:77-82.

59. Patel R, Blake GM, Fogelman I. An evaluation of the UK National Osteoporosis Society position statement on the use of peripheral dual-energy X-ray absorptiometry. Osteoporos Int 2004;15:497-504.

60. Siris ES, Chen E-T, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE, Berger ML. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 2004;164:1108-1112.

61. Wallace BA, Cumming RG. Systematic review of randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. Calcif Tissue Int 2000;67:10-18.

62. Kemmler W, Lauber D, Weineck J, Hensen J, Kalender W, Engelke K. Benefits of intense exercise on bone density, physical fitness, and blood lipids in early postmenopausal osteopenic women. Arch Intern Med 2004;164:1084-1091.

Angelo M. Taveira-DaSilva, Mario P. Stylianou, Carolyn J. Hedin, Olanda Hathaway, and Joel Moss

Pulmonary-Critical Care Medicine Branch and Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

(Received in original form June 2, 2004; accepted in final form September 29, 2004)

Supported by National Heart, Lung, and Blood Institute Intramural Research.

Correspondence and reprint requests should be addressed to Angelo M. Taveira-DaSilva, M.D., Ph.D., Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC 1590, Bethesda, MD 20892-1590. E-mail:

Am J Respir Crit Care Med Vol 171. pp 61-67, 2005

Originally Published in Press as DOI: 10.1164/rccm.200406-701OC on October 1, 2004

Internet address:

Conflict of Interest Statement: A.M.T-D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; M.P.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; C.J.H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; O.H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; J.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

Acknowledgment: The authors thank Drs. Martha Vaughan and Vincent Manganiello for their helpful discussions and critical review of the manuscript. They thank Xiaoling Chen for her assistance in compilation and analysis of the data, and they also thank the LAM Foundation and the Tuberous Sclerosis Alliance for their assistance in recruiting patients. This study would not have been possible without the cooperation of patients with LAM, who, in many cases, traveled great distances to participate in the clinical research protocols.

Copyright American Thoracic Society Jan 1, 2005
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