Endocrine Abstracts

Autoimmune pulmonary alveolar proteinosis (aPAP) is a disease whereby antibodies to granulocyte macrophage colony stimulating factor (GM-CSF) cause dysfunction of alveolar macrophages, leading to surfactant accumulation and respiratory failure. GM-CSF has a role outside the lung; promoting fusion of prefusion osteoclasts into multinucleated osteoclasts capable of bone resorption. Osteopetrosis is a disorder of reduced osteoclast function, causing failure of osteoclast-mediated resorption of the skeleton and increased fracture risk. We hypothesised that patients with aPAP may have low osteoclast activity as a result of GM-CSF dysfunction, mimicking osteopetrosis. This exploratory study phenotypes bone turnover in a cohort of patients with aPAP. Serum samples from 34 patients with aPAP from the Ruhrlandklinik, Essen were analysed for N-propeptide of type 1 collagen (P1NP) and C-terminal crosslinking telopeptide of type 1 collagen (CTX-1). 19 were male. Median age was 47.5 years (IQR 38.75-54). 8 patients were current smokers; 17 patients had previously smoked. 2 patients had a diagnosis of osteoporosis and 1 of myelodysplastic syndrome. 1 patient was on bisphosphonate therapy, 2 on hormone replacement therapy, and 5 were taking corticosteroids. P1NP levels in all participants with aPAP were within normal gender-specific reference ranges. Median P1NP in female patients was 41.60 mg/l (IQR 34.90-49.85 mg/l) (reference range 17.3-83.4 mg/l). Median P1NP in male patients was 39.2 mg/l (34.7-52.9 mg/l) (reference range 22.1-96.2 mg/l). The majority of the aPAP cohort demonstrated CTX-1 levels within normal reference ranges. Median CTX-1 in female patients was 0.22 mg/l (IQR 0.080-0.320 mg/l) (reference range 0.025-0.573). Median CTX-1 in male patients was 0.291 mg/l (0.205-0.380) (reference range 0.016-0.584). There was no difference in bone turnover markers in the aPAP cohort compared to 11 healthy controls (P1NP p-value = 0.56, CTX-1 p-value = 0.67). Bone turnover markers were normal in this cohort of aPAP patients. Further studies are required to establish if a relationship exists between aPAP and osteoclast dysfunction.