Bone mineral density in lymphangioleiomyomatosis.

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, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.04). 01/2005; 171(1):61-7. DOI: 10.1164/rccm.200406-701OC
Source: PubMed

ABSTRACT 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(2), p = 0.036) and T-scores (-0.050 +/- 0.041 vs. -0.191 +/- 0.041, p < 0.001) than untreated patients (n = 113). We conclude that abnormal BMD was frequent in LAM. Progesterone therapy was not associated with changes in BMD; bisphosphonate therapy was associated with lower rates of bone loss. We recommend systematic evaluation of BMD and early treatment with bisphosphonates for patients with LAM.

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    ABSTRACT: Lymphangioleiomyomatosis (LAM) is a progressive and usually fatal interstitial lung disease characterized by an abnormal smooth-muscle proliferation in the lung and axial lymphatics. It affects almost exclusively young women of childbearing age. The presenting features most commonly include dyspnea, symptoms of pneumothorax and cough. Less commonly patients can present with chest pain, pleural or pericardial effusion and lymphedema. Our patient, a 41-year-old woman, complained mainly of fatigue that had lasted for 2 months and finally became febrile and dispneic, especially when lying down. Pulmonary diagnostic procedures revealed several multicystic destruction of lung parenchyma. There was also respiratory insufficiency with O2 saturation of 87% and lung diffusion capacity reduced to 48%. The retroperitoneum was filled with neoplastic mass as shown on an abdominal CT scan. Pathohistologic analysis of retroperitoneal mass together with the radiologic finding of the lungs correlated with the diagnosis of LAM. The patient was prescribed corticosteroid therapy, which led to rapid clinical improvement. After making a definite diagnosis, the patient was recommended further treatment with medroxyprogesterone. This case shows that LAM, although rare, can present a diagnostic problem to clinicians and should always be considered as one of the diagnostic possibilities in young women with nonspecific pulmonary symptoms.
    Acta medica Croatica: c̆asopis Hravatske akademije medicinskih znanosti 02/2004; 58(3):233-6.
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    ABSTRACT: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disease of women of child-bearing age and affects mainly the lungs, promoting cystic destruction of lung parenchyma or leading to abdominal tumor formation (e.g., angiomyolipomas, lymphangioleiomyomas). LAM can arise sporadically or in association with tuberous sclerosis complex (TSC), an autosomal inherited syndrome characterized by hamartoma-like tumor growth and pathologic features that are distinct from manifestations of pulmonary LAM. A substantial body of evidence has now been gathered suggesting that the two diseases share a common genetic origin. TSC is caused by mutations in two genes, TSC1 on chromosome 9q34 and TSC2 on 16p13. Both of these genes are tumor suppressor genes encoding hamartin (TSC1) and tuberin (TSC2). Sporadic LAM is correlated with a mutation in the TSC2 gene and tuberin appears to play a central role in the pathogenesis of the disease. A TSC2 loss or mutation leads to disruption of the tuberin-hamartin heteromer and dysregulation of S6K1 activation leading to aberrant cell proliferation seen in LAM disease. The extremely diverse clinical and radiologic features of the disease and the complex therapeutic approach are reviewed in detail. Although new therapeutic agents have been tested, to date no effective treatment has been proposed and the prognosis of patients with LAM remains poor. As long as newer therapeutic agents do not change this picture, lung transplantation remains the last hope for patients with respiratory failure at the advanced stage of the disease.
    Beiträge zur Klinik der Tuberkulose 01/2008; 186(4):197-207. · 2.06 Impact Factor
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    ABSTRACT: Lymphangioleiomyomatosis is a rare and progressive lung cystic disease, caused by the infiltration of lung parenchyma by mesenchymal cells characterized by co-expression of contractile proteins and melanocytic markers. The pathogenesis of lymphangioleiomyomatosis is determined by mutations affecting tuberous sclerosis complex (TSC) genes, with eventual deregulation of the Rheb/mTOR/p70S6K pathway, and the potential therapeutic activity of mTOR inhibitors is currently under investigation. To better understand the molecular mechanisms involved in the pathogenesis of lymphangioleiomyomatosis, we investigated the expression of cathepsin-k (a papain-like cysteine protease with high matrix-degrading activity). The rationale of this choice was based on the recent demonstration that mTOR inhibitors can regulate major functional activities of osteoclasts, including the expression of cathepsin-k. The immunohistochemical study included 12 cases of lymphangioleiomyomatosis. Twelve angiomyolipomas and several lung diseases (sarcoidosis, organizing pneumonia, usual interstitial pneumonia, emphysema) were investigated as controls. In all lymphangioleiomyomatosis cases, strong cathepsin-k immunoreactivity was demonstrated, restricted to lymphangioleiomyomatosis cells. Similar expression levels were observed in renal angiomyolipomas. These observations extend the knowledge regarding the immunophenotypic profile of lymphangioleiomyomatosis cells, and provide a useful new marker for diagnosis in difficult cases (eg, in small transbronchial biopsies). The strong expression of such a potent papain-like cysteine protease in lymphangioleiomyomatosis cells can significantly contribute to the progressive remodelling of lung parenchyma observed in this deadly disease, with eventual formation of lung cysts. It is possible to speculate that mTOR inhibitors may exert part of their action by limiting the destructive remodelling of lung structure.
    Modern Pathology 01/2009; 22(2):161-6. · 5.25 Impact Factor


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