Jo-Anne Smith

Comparison of Serum and Urine Assays for Biochemical Markers of Bone Resorption in Postmenopausal Women with and without Hormone Replacement Therapy and in Men

Abstract: Biochemical markers of bone resorption have been used to characterize metabolic bone disease and assess therapeutic response. Most studies have used the urinary measurement of collagen crosslinks, but serum assays have recently been developed that may have less analytic and biologic variability. In the present study, we measured urine and serum N- and C-terminal crosslinked telopeptides of type I collagen (NTX and CTX) and serum bone sialoprotein (BSP) in postmenopausal women with or without hormone replacement therapy (HRT) and in men of similar age. In these populations, the variability of serum and urine markers was similar, except that serum NTX showed somewhat lower variability in postmenopausal women. Urine and serum assays correlated well with one another and were significantly lower in postmenopausal women on HRT compared with untreated women. The difference in women on HRT was similar for sNTX, uNTX and BSP (35–40%) and greater for sCTX and uCTX (52–53%). There was an inverse correlation between markers and bone mineral density, largely attributable to the high correlation in women not on HRT. Fractional excretion of NTX and CTX were estimated at 0.20 ± 0.07 and 0.44 ± 0.11, respectively. These values were independent of the concentration of the marker or of creatinine in the urine. We conclude that serum markers are useful measures of bone resorption in these populations, in whom the use of such markers is likely to be helpful in the management of osteoporosis.

Short-Term Risedronate Treatment in Postmenopausal Women: Effects on Biochemical Markers of Bone Turnover

Abstract: The development of new biochemical markers has made it possible to assess the effects of therapeutic agents on bone turnover more rapidly and precisely. In this early phase II study, we analyzed the effects of short-term, high-dose treatment with risedronate, a potent pyridinyl bisphosphonate, on markers of bone resorption and formation. Resorption markers included urinary free deoxypyridinoline (D-Pyr) crosslinks, N-terminal telopeptide (NTx) and C-terminal telopeptide (CTx) type I collagen crosslinks. Bone formation markers included osteocalcin (OC), bone-specific alkaline phosphatase (BSAP) and the C-terminal peptide of type I procollagen (PICP). All three resorption markers showed rapid, significant (p<0.05) decreases from baseline following daily administration of 30 mg risedronate for 2 weeks. The mean decreases at 2 weeks were 28% for D-Pyr, 61% for NTx and 73% for CTx, respectively. Over the next 10 weeks after treatment, D-Pyr approached baseline while NTx and CTx remained well below baseline values. The markers of bone formation showed little change during therapy but decreased significantly at 4–10 weeks after therapy – an expected outcome of bisphosphonate therapy. Moreover, there was a significant correlation between the early effects on bone resorption markers and the delayed effects on formation markers. This study demonstrates that the approved dose of risedonate (30 mg/day) for Paget”s disease is effective at decreasing bone turnover after 2 weeks of treatment, as observed by the sensitive response of bone turnover markers.

Aortic Calcification Contributing to Bone Densitometry Measurement

A 75-yr-old glucocorticoid-dependent asthmatic male had a bone mineral density study to assess possible osteoporosis prior to initiating therapy. A radiograph of the lumbar spine revealed an asymmetrical compression of the second lumbar vertebra, marked scoliosis, vertebral osteopenia, and a highly calcified abdominal aorta. Bone mineral density (dual X-ray absolptiometry [DXA]) revealed low bone mass in L2-L4 and a markedly abnonrnal pattern, with a linear central density representing a calcified aorta. Posterior-anterior measurements of the midlumbar region with and without the overlying aorta indicated that the calcified vessel contributed up to 33% of the measured density. This was a far higher contribution than reported in other studies. Lateral DXA measurements of the L2 vertebra and the overlying aorta were performed to validate this finding. The density of the L2 vertebra was 0.215 g/cm(2), and that of the overlying calcified aorta was 0. 210 g/cm(2). This case suggests that aortic calcifications may contribute sign)ficantly to overall lumbar bone density and, unless recognized, can inadvertently lead to misclassification of osteoporosis.

Diagnosis of osteoporosis

Early diagnosis is the key to the prevention and treatment of osteoporosis. A healthy skeleton has intrinsic properties that confer strength to resist fracture under ordinary stress. Some of the properties that confer strength and fracture resistance include: bone mass or density and bone quality determined by skeletal composition, fine structure and spatial organization, geometric properties, and rate of remodeling. The current approach to early diagnosis of osteoporosis is based on the measurement of bone mass or bone mineral density (BMD). Low bone mass is the single most accurate predictor of increased fracture risk. BMD accounts for 70% to 80% of the future fracture risk in older white women and is a far better predictor of osteoporosis than hypertension is for stroke or total cholesterol is for cardiovascular events in men. Perhaps in the future a better understanding and quantification of bone quality will help refine our ability to identify patients at risk. BMD can be measured at a variety of skeletal sites using several different methods that have been approved by the FDA. The basic attributes of each method will be addressed in this paper, with particular attention given to the method that is currently considered the gold standard, dual energy x-ray absorptiometry. The indications for BMD testing, clinical utility of BMD, frequency of follow-up testing, correlation between the available densitometry methods, problems and pitfalls in interpretation, and features of a satisfactory densitometry report of results will all be addressed. The current role of biochemical markers of bone turnover in the diagnosis and monitoring of treatment will be discussed briefly.

Osteoporosis Risk in Frail Older Adults in Assisted Living

OBJECTIVES: To compare osteoporosis risk in residents of assisted living (AL) with that of age‐ and sex‐matched community‐dwelling adults.

Adherence of academic geriatric practitioners to osteoporosis screening guidelines

ObjectivesTo examine the bone mineral density (BMD) testing habits of geriatricians and geriatric fellows at the University of Connecticut fellowship training program to evaluate their adherence screening guidelines.DesignRetrospective chart review.SettingUniversity based academic geriatric practice in Farmington, CT.ParticipantsChart review of two hundred female patients over age 65 under care of seven faculty geriatricians and eight geriatric fellows in training.MeasurementsData collected included BMD testing status, patient’s osteoporosis risk factors and functional status.ResultsPhysicians ordered BMD tests in 151 (76%) patients; 128 (64%) had a bone mineral density test within three years. A personal history of fracture was the only osteoporosis risk factor that correlated to higher rates of osteoporosis testing. Physicians were more likely to order BMD screening in younger patients (92% in 65–74 vs. 74% in ages 85+, P=.031), patients independent in activities of daily living (72% vs. 32, P=.002), and patients without dementia (70% vs.37%, p=.007). BMD testing results found 82% with osteopenia or osteoporosis.ConclusionsA geriatric group that is highly attuned to bone health demonstrated more optimal adherence to OP testing guidelines for all “at-risk” older women and better than reported previously. Functional status more strongly predicted BMD testing than osteoporosis risk factors. This study suggests that with improved physician education and familiarity with the disease, high rates of BMD testing for earlier identification of geriatric patients at risk for osteoporosis are achievable.

Gall Stones Detected on Lumbar Bone Densitometry Examination

A dual-energy X-ray bone densitometry study, in a 73-yr-old woman, detected gall stones in the right upper quadrant of the abdomen. These showed a rim of higher density. The density of the region was 0.550 g/cm2, or 70% of the value found in the L1 vertebra.