Misdiagnosis and Mistreatment of a Rare Case of Intracranial Oncogenic Osteomalacia with an Altered Amino Acid Profile.

Background. Oncogenic osteomalacia (OO), also known as tumor-induced osteomalacia (TIO), is a rare paraneoplastic syndrome caused by mesechymal tumors secreting fibroblast growth factor 23 (FGF23). Common in middle age, these tumors are often disclosed by progressive generalized bone pain and muscle weakness, along with an altered biochemical profile. Despite its characteristic presentation, the disease is often underrecognized with delayed onset of surgical or pharmacological intervention that can have serious repercussions on the patients' health and quality of life. Case presentation. We describe the case of a 65-year-old Caucasian man presenting TIO with intracranial and spinal localizations and Fanconi-like aminoaciduria. The condition was misdiagnosed and mistreated for three years, leading to loss of self-sufficiency and depression. Following proper identification, the spinal mass was excised with complete remission of the functional symptoms. As it was not possible to remove the intracranial lesion, the patient was treated conservatively with calcitriol and phosphorous supplements that granted good metabolic control up to the time of a recent follow-up visit (at 5 years). Conclusions. The finding of an altered amino acid profile, not usually reported in these cases, should prompt clinicians to a wider usage of these molecules as suitable candidates for metabolic diseases. In addition to providing central information, they are easy to obtain and inexpensive to analyze. Such determination could help to speed up the diagnostic process, as a long-lasting history of misdiagnosis and mistreatments can lead primarily to clinical worsening, but also to the use of expensive, useless medications with side effects that contribute to poor patient health.

Further insights about the beneficial effects of n-3 fatty acids in the early molecular events of renal fibrosis in vitro.

BACKGROUND: Accumulating experimental and clinical evidence reveals beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) in kidney disease by modulating inflammation and fibrosis mechanisms that lead to renal failure. METHODS: EPA, DHA (n-3 PUFAs) and AA (n-6 PUFA) effects, compared to those of AngII, on renal fibrotic processes at the extracellular matrix (ECM) level were verified in human mesangial cells in vitro, by means of RT-PCR, mitogenic assay and Western-blot analysis. RESULTS: Unlike AngII, EPA and DHA enhanced the expression of MMP2 and DN, a TGFbeta inhibitor, while decreasing mitogenic factors such as PDGF and bFGF, and cell proliferation. Moreover, n-3 PUFAs elicited Bax expression in AngII-treated cells and downregulated COX-2--an enzyme involved in the inflammatory cascade. The mechanism of action could implicate PPARgamma activation, as this transcription factor was shown to translocate to the nucleus upon n-3 PUFA treatment. CONCLUSIONS: These results complement our previous reports demonstrating that EPA and DHA prevent ECM accumulation and inflammation that typify the fibrotic process, providing new insights into the cellular and molecular mechanisms underlying their beneficial effects. We confirm that n-3 PUFAs could effectively counteract kidney fibrosis development providing a rationale for their use in clinical settings.

Vitamin D and physical performance in elderly subjects: the Pro.V.A study.

BACKGROUND: The role of Vitamin D in musculoskeletal functionality among elderly people is still controversial. We investigated the association between serum 25-hydroxyvitamin D (25OHD) levels and physical performance in older adults. METHODS: 2694 community-dwelling elderly women and men from the Progetto Veneto Anziani (Pro.V.A.) were included. Physical performances were assessed by: tandem test, 5 timed chair stands (TCS), gait speed, 6-minute walking (6 mW) distance, handgrip strength, and quadriceps strength. For each test, separate general linear models and loess plots were obtained in both genders, in relation to serum 25OHD concentrations, controlling for several potential confounders. RESULTS: Linear associations with 25OHD levels were observed for TCS, gait speed, 6 mW test and handgrip strength, but not for tandem test and quadriceps strength. After adjusting for potential confounders, linear associations with 25OHD levels were still evident for the 6 mW distance in both genders (p = .0002 in women; <.0001 in men), for TCS in women (p = .004) and for gait speed (p = .0006) and handgrip strength (p = .03) in men. In loess analyses, performance in TCS in women, in gait speed and handgrip strength in men and in 6 mW in both genders, improved with increasing levels of 25OHD, with most of the improvements occurring for 25OHD levels from 20 to 100 nmol/L. CONCLUSION: lower 25OHD levels are associated with a worse coordination and weaker strength (TCS) in women, a slower walking time and a lower upper limb strength in men, and a weaker aerobic capacity (6 mW) in both genders. For optimal physical performances, 25OHD concentrations of 100 nmol/L appear to be more advantageous in elderly men and women, and Vitamin D supplementation should be encouraged to maintain their 25OHD levels as high as this threshold.

Intramuscular neridronate in postmenopausal women with low bone mineral density.

Compliance to osteoporosis treatment with oral bisphosphonates is very poor. Intermittent intravenous bisphosphonate is a useful alternative, but this route is not readily available. Neridronate, a nitrogen-containing bisphosphonate that can be given intramuscularly (IM), was tested in a phase 2 clinical trial in 188 postmenopausal osteoporotic women randomized to IM treatment with 25 mg neridronate every 2 weeks, neridronate 12.5 or 25 mg every 4 weeks, or placebo. All patients received calcium and vitamin D supplements. The patients were treated over 12 months with 2-year posttreatment follow-up. After 12-month treatment, all three doses were associated with significant bone mineral density (BMD) increases at both the total hip and spine. A significant dose-response relationship over the three doses was observed for the BMD changes at the total hip but not at the spine. Bone alkaline phosphatase decreased significantly by 40-55% in neridronate-treated patients, with an insignificant dose-response relationship. Serum type I collagen C-telopeptide decreased by 58-79%, with a significant dose-response relationship (P < 0.05). Two years after treatment discontinuation, BMD declined by 1-2% in each dose group, with values still significantly higher than baseline at both the spine and the total hip. Bone turnover markers progressively increased after treatment discontinuation, and on the second year of follow-up the values were significantly higher than pretreatment baseline. The results of this study indicate that IM neridronate might be of value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusion of bisphosphonates.