Global urinary metabolic profiling of the osteonecrosis of the femoral head based on UPLC-QTOF/MS.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH), one of the widespread orthopedic diseases with a decrease in bloodstream to the femoral head, is frequently accompanied by cellular death, trabecula fracture, and collapse of the articular surface. The exactly pathological mechanism of ONFH remains to explore and further identify. OBJECTIVES: The aim was to identify the global urinary metabolic profiling of ONFH and to detect biomarkers of ONFH. METHODS: Urine samples were collected from 26 ONFH patients and 26 healthy people. Ultra-performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS) in combination with multivariate statistical analysis was developed and performed to identify the global urinary metabolic profiling of ONFH. RESULTS: The urinary metabolic profiling of ONFH group was significantly separated from the control group by multivariate statistical analysis. 33 distinctly differential metabolites were detected between the ONFH patients and healthy people. Sulfate, urea, Deoxycholic acid and PE(14:0/14:1(9Z)) were screened as the potential biomarkers of ONFH. In addition, the up/down-regulation of sulfur metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, and histidine metabolism were clearly be associated with the ONFH pathogenic progress. CONCLUSION: Our results suggested that metabolomics could serve as a promising approach for identifying the diagnostic biomarkers and elucidating the pathological mechanism of ONFH.

Biomarkers of bone remodeling in multiple myeloma patients to tailor bisphosphonate therapy.

BACKGROUND: Patients with multiple myeloma may be susceptible to osteonecrosis of the jaw (ONJ) and stress fractures due to long-term aminobisphosphonate (aBP) therapy. However, it is unknown whether urinary N-telopeptide (NTX) or other bone biomarkers are predictive of skeletal-related events (SRE) or the impact of cessation of aBP therapy on bone remodeling. METHODS: We studied markers of bone turnover over a 6-month period after a single dose of zoledronic acid in 29 patients with multiple myeloma in remission who previously received 8 to 12 doses of pamidronate or zoledronate (NCT00577642). Our primary objective was to determine the duration of time urinary NTX levels remain suppressed after a single dose of zoledronate. A secondary objective was to identify and correlate other markers of bone remodeling with NTX changes. Thirty cytokines, based on their possible role in bone remodeling, were tested using cytokine arrays. Candidates were confirmed by ELISA. RESULTS: All patients had continued suppression of NTX levels, except 1 patient who had an increase in NTX levels associated with an SRE. GDF-15 and decorin were found to decrease, whereas bone-specific alkaline phosphatase (BSALP) increased. Although not significant in aggregate, osteopontin and osteoprotegerin levels increased in at least half of the patients. CONCLUSION: Our data show that NTX levels continue to be suppressed after aBP therapy, and suggest that suppressed NTX levels may be predictive of freedom from SRE in this patient population. Furthermore, osteoblast suppression by aBP may be reversible in myeloma. These data provide the basis for less frequent dosing of aBPs.

Bone necrosis and urinary hydroxyproline excretion in rabbits.

1. Aseptic necrosis of bone is a serious chronic complication of deep-sea diving and compressed-air work. 2. The changes to the bone which occur in this condition take time to develop to the stage where they cause the radiographic signs of bone necrosis, and consequently there is a delay of some months between the causal incident and the first diagnosis by radiography. 3. As a possible method for the earlier detection of bone necrosis the 24 h urinary excretion of hydroxyproline was measured over a period before and after experimental production of bone necrosis in rabbits by the intra-arterial injection of glass microspheres. 4. Total hydroxyproline excretion rose significantly within a few days of the injection in those rabbits in which there was later shown to be historical evidence of bone necrosis. This rise occurred long before there was any radiographic changes. 5. It is suggested that measurements of urinary hydroxyproline might be used to give an early indication of bone necrosis in man.