Calcium and vitamin D supplementation: when and why.

Osteoporosis is a common disease, with fragility fractures representing its dreaded complications. The role of calcium and vitamin D supplementation needs to be addressed in the context of a heavy health burden, with a massive impact on individuals, healthcare systems, and societies as a whole. Calcium and vitamin D are often discussed together as interventions for promoting bone health. Still, it is essential to remember that they are quite distinct entities that play different roles in mineral metabolism. Insufficient calcium intake and vitamin D deficiency are common and widespread. Furthermore, a strong association between vitamin D deficiency and extra-skeletal outcomes has emerged over the last decades. When dietary intake is insufficient, with little room for improvement, several supplementation strategies have proved to be effective and safe. Adequate calcium intake and vitamin D serum levels should be pursued efficiently in the general population, and deficiency should be considered unacceptable in subsets particularly at risk. The aim of this narrative review was to present an overview of calcium and vitamin D intake and their supplementation.

Is central sensitization an important determinant of functional disability in patients with chronic inflammatory arthritides?

BACKGROUND: Central sensitization (CS) is a condition characterized by a disproportionate response to pain stimuli. We sought to investigate the prevalence of CS in patients with inflammatory arthritides and its association with measures of disease activity and functional disability. METHODS: We conducted an observational retrospective study in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients. We administered to all the subjects in the study the CS inventory (CSI), a questionnaire that has been used for the diagnosis of CS. Demographic and clinical characteristics were collected as well as measures or disease activity [i.e. Simple Disease Activity Index, Disease Activity Score in PsA (DAPSA)] and functional disability [Health Assessment Questionnaire Disability Index (HAQ-DI)]. Patients with fibromyalgia were excluded from the analyses. The primary outcome measure was the presence of functional disability as assessed by HAQ-DI >1. RESULTS: We enrolled 150 patients with inflammatory arthritides (78 PsA and 72 RA). Prevalence of CS was observed in 35.3% of the overall sample (29% in RA, 42.9% in PsA). Binary logistic regressions showed a strong, independent and linear association between functional disability and CS in both PsA and RA patients. The strength of this association was greater in PsA than in RA. CONCLUSION: CS is an important determinant of functional disability in patients with chronic inflammatory arthritides. PsA appeared to be more vulnerable to CS. In addition, in the presence of CS, DAPSA did not adequately capture the occurrence of functional disability. Therefore, special attention should be paid to PsA patients, in whom the concomitant diagnosis of CS should be routinely ruled out.

Wnt Inhibitors and Bone Turnover Markers in Patients With Polymyalgia Rheumatica and Acute Effects of Glucocorticoid Treatment.

Background: In polymyalgia rheumatica (PMR), data on bone turnover markers (BTM), on Wnt inhibitors (Dkk-1, sclerostin) and their changes induced by glucocorticoids (GC) are lacking. The aims of our study were to compare the baseline levels of Wnt inhibitors and BTM in PMR patients with healthy controls (HC) and to study their changes over the first 4 weeks of GC treatment. Materials and Methods: We enrolled 17 treatment-naïve patients affected by PMR and 17 age and sex-matched healthy controls (HC) from retired hospital personnel. PMR patients were administered methylprednisolone 16 mg daily for 4 weeks. Blood samples were taken at baseline and at week 4 for the PMR group, a single sample was taken for HC. N-propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (CTX-I), sclerostin, Dkk-1, and C-reactive protein (CRP) were dosed. Results: At baseline, Dkk-1 was significantly higher in the PMR group as compared to HC (p = 0.002) while PINP, CTX-I and sclerostin levels were comparable between PMR patients and HC, After 4 weeks of GC treatment we found in the PMR group a decrease of PINP (mean ± SD percentage decrement as compared to baseline -40 ± 18.6%, p < 0.001), CTX-I (-23.5 ± 41.3%, p = 0.032), Dkk-1 (-22.4 ± 39.6, p = 0.033), and sclerostin (-32.49 ± 20.47, p < 0.001) as compared to baseline levels. Conclusions: In treatment-naïve PMR, systemic inflammation is associated with a dysregulation of the Wnt system (increased Dkk-1). Within the 1st month, treatment with GC showed noteworthy effects on bone resorption, formation, and on Wnt pathway modulators.

Correction to: The ultrasonographic study of the nail reveals differences in patients affected by inflammatory and degenerative conditions.

The original published version of this article contained the incorrect Table 2 and are now presented correctly in this article.

The ultrasonographic study of the nail reveals differences in patients affected by inflammatory and degenerative conditions.

INTRODUCTION AND OBJECTIVES: The nail unit is a subject of interest in several diseases, often involving different medical fields. Even if few data are available for psoriasis and psoriatic arthritis, no data regarding ultrasonography and imaging are present for other degenerative and inflammatory conditions. The aim of this study was to explore through imaging the changes of nail and enthesis in inflammatory and degenerative conditions in order to find qualitative and quantitative changes related to distal interphalangeal joints. METHODS: The study sample was composed of 51 patients affected by psoriatic arthritis, 31 affected by psoriasis, 37 subjects with rheumatoid arthritis, 34 with osteoarthritis and 50 healthy controls for a total of 203 individuals. Ultrasonography of the nails was performed after clinical evaluation in a cross-sectional study design by blinded ultrasonographers who were blind to patient data. Data about power Doppler signal of the nail bed, tendon entheses, thickness of nail plate and nail bed were recorded. RESULTS: Patients affected by psoriasis and psoriatic arthritis differ from other subgroups, and power Doppler signal at the enthesis seems to be an exclusive feature of psoriatic arthritis (Pearson's chi-square of 5297 and p < 0.001 with adjusted residuals). Nail plate thickness also differs in psoriasis and psoriatic arthritis, but surprisingly in osteoarthritis, too, with similar results. CONCLUSIONS: This study provides qualitative and quantitative data regarding the ultrasonographic features of nails in several rheumatic diseases with a potential role of ultrasonography in characterising them.

New Strategies for the Prevention and Treatment of Systemic and Local Bone Loss; from Pathophysiology to Clinical Application.

Bone loss is the result of a negative unbalance between bone formation ad bone resorption. In the last years, the studies on the Wnt canonical pathway have highlighted its crucial role in bone balance through its influence on the activity and maturation of the osteoblast line and in the Receptor Activator of Nuclear Factor κ B (RANK) - RANK ligand (RANKL)/Osteoprotegerin (OPG) system. These mechanisms are involved not only in the pathological processes inducing not only systemic bone loss (i.e. Postmenopausal osteoporosis, glucocorticoid- induced osteoporosis, etc.), but also at a local level, as happens in Rheumatoid Arthritis (RA). Recently, several new drugs for the treatment of bone loss have been approved, while some others are still under development. The most promising new drugs in the treatment of osteoporosis include the antibody that neutralizes RANKL (denosumab, DMAb), monoclonal antibodies against sclerostin and parathyroid hormone-related protein analogue. Other new strategies for the prevention and treatment of bone loss include calcilytics, cathepsin K inhibitor or the combination or the sequential use of the current drugs. New insights concerning the treatment of the local bone loss in RA and in Complex Regional Pain Syndrome type I are also provided in this review.

In psoriatic arthritis Dkk-1 and PTH are lower than in rheumatoid arthritis and healthy controls.

Psoriatic Arthritis (PsA) is characterized by bone erosive damage often associated with exuberant bone formation especially in enthesial sites. Dkk-1 and sclerostin are the main inhibitors of the WNT/ß-catenin signaling pathway and play a key role in the regulation of both bone formation and resorption. We performed this study in order to compare the serum levels of the WNT-pathway regulators along with bone turnover markers (BTM) and parathyroid hormone (PTH) between three different groups: one group of female patients affected by PsA, one group of female patients affected by rheumatoid arthritis (RA), and healthy female controls (HC). This is a cross-sectional study including 33 patients with PsA classified with the CASPAR criteria, 35 HC, and 28 patients with RA classified with the ACR/EULAR 2010 criteria. Intact N-propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (CTX-I), Dickkopf-related-protein 1 (Dkk-1), sclerostin, PTH, and 25OH-vitamin D serum levels were dosed. The PsA group showed significantly lower Dkk-1 levels when compared to the HC and RA groups. Dkk-1 in the RA group was significantly higher than HC. A similar trend was documented for PTH. In the PsA group, CTX-I was found to be lower than in both the RA and HC groups. This study demonstrated for the first time that Dkk-1 levels in PsA are lower than HC, in contrast with RA, in which they are increased. These results might contribute to explain the different bone involvement of the two different diseases.

18F-fluoride PET/CT for detection of axial involvement in ankylosing spondylitis: correlation with disease activity.

OBJECTIVES: Aim of the current study was to evaluate the relationships between the findings of 18F-fluoride PET/CT (F-PET/CT) reflecting osteo-proliferative processes and the clinical indexes related to the disease activity. The clinical indexes are Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). METHODS: We studied 29 AS patients aged 26-69 years with a wide range of disease activity using F-PET/CT. The number of regions of high bone turnover or osteoarthritis features at the spine and at sacroiliac joints was counted. RESULTS: The number of F-PET/CT positive sites was significantly higher in patients with severe functional impairment and higher disease activity and it was positively related to both BASDAI (r = 0.336; P = 0.036) and ASDAS (r = 0.408; P = 0.014) while the number of degenerative features (osteoarthritis) was related neither with functional impact nor with disease activity. CONCLUSIONS: With a single examination, F-PET/CT accurately identifies the functional impairment and the clinical involvement of AS. The good correlation we found between the number of F-PET/CT positive sites and disease activity candidates this technique also for follow-up of AS.