Identification of subclinical lung involvement in ACPA-positive subjects through functional assessment and serum biomarkers

Lung involvement is related to the natural history of anti-citrullinated proteins antibodies (ACPA)-positive rheumatoid arthritis (RA), both during the pathogenesis of the disease and as a site of disease-related injury. Increasing evidence suggests that there is a subclinical, early lung involvement during the course of the disease, even before the onset of articular manifestations, which can potentially progress to a symptomatic interstitial lung disease. To date, reliable, noninvasive markers of subclinical lung involvement are still lacking in clinical practice. The aim of this study is to evaluate the diagnostic potential of functional assessment and serum biomarkers in the identification of subclinical lung involvement in ACPA-positive subjects. Fifty ACPA-positive subjects with or without confirmed diagnosis of RA (2010 ARC-EULAR criteria) were consecutively enrolled. Each subject underwent clinical evaluation, pulmonary function testing (PFT) with assessment of diffusion lung capacity for carbon monoxide (DLCO), cardiopulmonary exercise testing (CPET), surfactant protein D (SPD) serum levels dosage and high-resolution computed tomography (HRCT) of the chest. The cohort was composed of 21 ACPA-positive subjects without arthritis (ND), 10 early (disease duration < 6 months, treatment-naïve) RA (ERA) and 17 longstanding (disease duration < 36 months, on treatment) RA (LSRA). LSRA patients had a significantly higher frequency of overall HRCT abnormalities compared to the other groups (p = 0.001). SPD serum levels were significantly higher in ACPA-positive subjects compared with healthy controls (158.5 ± 132.3 ng/mL vs 61.27 ± 34.11 ng/mL; p < 0.0001) and showed an increasing trend from ND subjects to LSRD patients (p = 0.004). Patients with HRCT abnormalities showed significantly lower values of DLCO (74.19 ± 13.2% pred. vs 131.7 ± 93% pred.; p = 0.009), evidence of ventilatory inefficiency at CPET and significantly higher SPD serum levels compared with subjects with no HRCT abnormalities (213.5 ± 157.2 ng/mL vs 117.7 ± 157.3 ng/mL; p = 0.018). Abnormal CPET responses and higher SPD levels were also associated with specific radiological findings. Impaired DLCO and increased SPD serum levels were independently associated with the presence of HRCT abnormalities. Subclinical lung abnormalities occur early in RA-associated autoimmunity. The presence of subclinical HRCT abnormalities is associated with several functional abnormalities and increased SPD serum levels of SPD. Functional evaluation through PFT and CPET, together with SPD assessment, may have a diagnostic potential in ACPA-positive subjects, contributing to the dentification of those patients to be referred to HRCT scan

Osteomalacia and Vitamin D Status: A Clinical Update 2020

Historically, rickets and osteomalacia have been synonymous with vitamin D deficiency dating back to the 17th century. The term osteomalacia, which literally means soft bone, was traditionally applied to characteristic radiologically or histologically documented skeletal disease and not just to clinical or biochemical abnormalities. Osteomalacia results from impaired mineralization of bone that can manifest in several types, which differ from one another by the relationships of osteoid (ie, unmineralized bone matrix) thickness both with osteoid surface and mineral apposition rate. Osteomalacia related to vitamin D deficiency evolves in three stages. The initial stage is characterized by normal serum levels of calcium and phosphate and elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D]—the latter a consequence of increased PTH. In the second stage, serum calcium and often phosphate levels usually decline, and both serum PTH and alkaline phosphatase values increase further. However, serum 1,25(OH)2D returns to normal or low values depending on the concentration of its substrate, 25-hydroxyvitamin D (25OHD; the best available index of vitamin D nutrition) and the degree of PTH elevation. In the final stage, hypocalcemia and hypophosphatemia are invariably low with further exacerbation of secondary hyperparathyroidism. The exact,or even an approximate, prevalence of osteomalacia caused by vitamin D deficiency is difficult to estimate, most likely it is underrecognized or misdiagnosed as osteoporosis. Signs and symptoms include diffuse bone, muscle weakness, and characteristic fracture pattern, often referred to as pseudofractures, involving ribs, scapulae, pubic rami, proximal femurs, and codfish-type vertebrae. The goal of therapy of vitamin D-deficiency osteomalacia is to alleviate symptoms, promote fracture healing, restore bone strength, and improve quality of life while correcting biochemical abnormalities. There is a need for better understanding of the epidemiology of osteomalacia. Simplified tools validated by concurrent bone histology should be developed to help clinicians promptly diagnose osteomalacia

How to define an osteoporotic vertebral fracture?

A vertebral deformity (VD) is not always a vertebral fracture (VF). Because of lack of a completely satisfactory “gold standard”, there is no consensus on the exact definition of a VF. Therefore, it may sometimes be difficult, especially in mild cases, to discriminate the prevalent VF from a non-fracture deformity or short vertebral height (SVH). A combined standardized approach based on qualitative and semiquantitative (SQ) vertebral assessment may be the most option to correctly identify a VD as a VF. However this visual approach for VF identification is subjective, therefore it is mandatory an adequate training and experience of radiologist to reach a good sensitivity and specificity. Vertebral morphometry, objective and reproducible method, could be used only to evaluate the severity of VFs but requires the availability of reference values of vertebral height ratios. There is actually an evidentiary basis for suggesting that a qualitative approach by expert radiologists to morphological vertebral assessment, combined SQ and morphometric methods seem to be the preferred option for the correct diagnosis of VF as endplate or/and cortex fracture (ECF) or severe vertebral height loss

Vertebral Morphometry

Visual semiquantitative (SQ) assessment of the radiographs by a trained and experienced observer is the " gold standard" method to detect vertebral fractures. Vertebral morphometry is a quantitative method to identify osteoporotic vertebral fractures based on the measurement of vertebral heights. Vertebral morphometry may be performed on conventional spinal radiographs (MRX: morphometric x-ray radiography) or on images obtained from dual x-ray absorptiometry (DXA) scans (MXA: morphometric x-ray absorptiometry). Vertebral fracture assessment (VFA) indicates the method for identification of the vertebral fractures using lateral spine views acquired by DXA, with low-dose exposition. For epidemiologic studies and clinical drug trials in osteoporosis research but also in clinical practice, the preferred method is radiographic SQ assessment., because an expert eye can better distinguish between true fractures and vertebral anomalies than can quantitative morphometry. However, vertebral morphometry, calculating the deformity of overall thoracic and lumbar spine, may supply useful data about the vertebral fracture risk. VFA performed during routine densitometry allows identification, by visual or morphometric methods, of most osteoporotic vertebral fractures, even those that are asymptomatic. © 2010