Current assays overestimate 25-hydroxyvitamin D3 and underestimate 25-hydroxyvitamin D2 compared with HPLC: need for assay-specific decision limits and metabolite-specific assays.

BACKGROUND: Clinical demand for quick, cheap, precise and accurate 25-hydroxyvitamin D (25(OH)D) results has led to the development of a variety of assay methods. Lack of standardization of these methods has resulted in inter-method disagreement and challenged whether current assays recognize 25(OH)D2 and 25(OH)D3 equally. METHODS: We studied 172 patient samples from hip fracture cases using DiaSorin (DS) and IDS radioimmunoassays and the Nichols Advantage-automated protein binding assay (NA-CLPBA) in comparison to high-performance liquid chromatography (HPLC). 52 patient samples were analysed before and after three months treatment with 1000 IU of daily ergocalciferol (vitamin D2). RESULTS: Linear regression analysis in pre-treatment samples demonstrated a positive Y-intercept for each immunoassay compared with HPLC, and a slope that varied from 0.64 (IDS) to 0.97 (DS, NA-CLPBA). Bland Altman analysis demonstrated that all the three assays had a proportional positive bias relative to HPLC at values from 20 to 50 nmol/L. Regression analysis of post-treatment samples demonstrated a slope that was not significantly different from zero for the IDS and NA-CLPBA and 0.2 for the DS method, with a positive intercept for all assays of between 8 and 22, indicating less than 50% of 25(OH)D2 measured by HPLC was detected. CONCLUSIONS: These results demonstrate the need for assay-specific decision limits for 25(OH)D3 in order to define appropriate thresholds for treatment institution. Treatment with vitamin D2 may not be accurately monitored with any of the three commercial assays studied. Clinicians and biochemists who continue to use 25(OH)D assays need to be urgently informed of these issues.

Hip fracture outcomes: quality of life and functional status in older adults living in the community.

BACKGROUND: People who return to living in the community after a hip fracture are considered to have the best outcome. However, their quality of life (QOL) and its relationship with function over the longer term have not been fully assessed. AIMS: This case control study of community dwelling subjects six to 12 months post hip fracture aims to investigate their QOL and functional independence. METHOD: The Short Form-36 (SF-36) was utilised to measure QOL. The Modified Barthel Index (MBI), the Frenchay Activities of Daily Living Index (FAI), the Timed 'Up & Go' (TUG), and the Berg Balance Scale (Berg) were used to measure functionality. RESULTS: Ninety-two subjects and 92 controls were recruited. Despite being age and gender matched, the hip fracture subjects scored significantly (p<0.05) worse than the controls in all measures of function. The fracture group was slower on the TUG (19 vs 10.5 seconds), had more difficulties with balance (46 vs 54 out of 56), and was less active and more dependent than the control group (FAI 24 vs 31 out of 42). The SF-36 has eight domains: physical function, role physical, bodily pain, mental health, role emotional, social function, general health and vitality. The control group had a higher (p<0.05) perception of their QOL in all domains. CONCLUSION: The effects of impaired balance and mobility along with reduced functional and social independence are reflected in the diminished QOL perceived by the fracture group. This indicates that many do not return to their pre-fracture lifestyle.

Secondary hyperparathyroidism in patients from Western Australia with hip fracture: relationship to type of hip fracture, renal function, and vitamin D deficiency.

OBJECTIVES: To determine the frequency of vitamin D deficiency and secondary hyperparathyroidism in Australian hip fracture patients living in the community. PATIENTS: A total of 283 consecutive patients with hip fracture admitted over a 15-month period to a university teaching hospital in Western Australia. Included were residents of hostels for the elderly, and excluded were nursing home residents and those with malignant fractures. METHOD: Data collected included biochemistry (25 hydroxyvitamin D, parathyroid hormone and creatinine levels), measurements of function and disability (Barthel Index, Frenchay Activity Index), sunshine exposure, and basic demographics. RESULTS: Vitamin D deficiency occurred in 31.7% and secondary hyperparathyroidism occurred in 17.7% of cases. The major determinants of vitamin D deficiency were outdoor sunshine exposure, ambient daily sunshine, and disability (low Frenchay Activity Index or ADL difficulty). Secondary hyperparathyroidism was related to older age, renal dysfunction, and vitamin D deficiency. Secondary hyperparathyroidism was associated with an excess of trochanteric over subcapital hip fractures. CONCLUSIONS: Secondary hyperparathyroidism appears to be a heterogeneous condition, caused in approximately equal proportions by vitamin D deficiency and renal dysfunction, that may confer increased cortical bone fragility and trochanteric fractures. Renal dysfunction in old age may be an important additional determinant of senile osteoporosis, which has implications for preventive therapy. Vitamin D deficiency occurs in disabled and, presumably, housebound older people despite near optimal climatic conditions.

Neuroleptic malignant syndrome complicating levodopa withdrawal.

OBJECTIVE: To describe a case of neuroleptic malignant syndrome (NMS) resulting from withdrawal of low-dose levodopa therapy for mild Parkinson's disease. CLINICAL FEATURES: Treatment with levodopa, 50 mg, and benserazide, 12.5 mg, three times a day was withdrawn from a 76-year-old woman with mild Parkinson's disease because she was experiencing intermittent confusion. Fever (38.5 degrees C), tachycardia, increased confusion, severe rigidity and generalised stimulus-sensitive myoclonus developed after 12 hours. The creatine kinase level rose to 2058 U/L. INTERVENTION AND OUTCOME: The fever abated with reintroduction of levodopa. Rigidity was slow to resolve and required additional treatment with dantrolene sodium. CONCLUSION: NMS may be precipitated by withdrawal of relatively low doses of levodopa, even in patients with mild Parkinson's disease. Hyperthermia and rigidity in NMS may result from involvement of separate central dopaminergic pathways.