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Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry. Methods We obtained fasting blood samples from 69 patients with CKD stages 4–5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD. Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested. Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.

Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high- or low-turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients.

Objective— Epidemiological studies link higher serum phosphate and the phosphatonin fibroblast growth factor 23 with cardiovascular events and atheroma, and they link lower serum phosphate with insulin resistance and the metabolic syndrome. We investigated whether manipulating dietary phosphate influences atherogenesis or insulin sensitivity in mice. Methods and Results— Apolipoprotein E knockout mice were fed an atherogenic diet with low (0.2%), standard (0.6%), or high (1.6%) phosphate content. Serum phosphate and fibroblast growth factor 23 significantly increased with increasing dietary phosphate intake, but lipid profile and blood pressure were unaffected. After 20 weeks, mice on the higher phosphate diet had significantly more atheroma at the aortic sinus (42±1.9% versus 30±1.5% for high versus low phosphate, P P Conclusion— A high-phosphate diet accelerates atherogenesis in apolipoprotein E −/− mice, whereas low phosphate intake induces insulin resistance. These data indicate for the first time that controlling dietary phosphate intake may influence development of both atherosclerosis and the metabolic syndrome.

Glucocorticoids remain a key component in the management of many inflammatory disorders but the adverse consequences, especially on bone, can be devastating. The incidence of glucocorticoid-induced osteoporosis (GIO) may be as high as 50% after 6 months' treatment with steroids. This manifests itself as a 30 to 400% increase in the incidence of low trauma fractures. The incidence rates can be even greater in specific clinical settings such as following organ transplantation. The pathogenesis of glucocorticoid-induced osteoporosis remains complex and perplexing.The concomitant prescription of bone-active drugs for the prevention and treatment of GIO in the United Kingdom population remains low, despite the availability of effective therapies. In addition, there remain many unanswered questions about the pathogenesis of GIO and clinical management. These include identification of the optimum bone mineral density threshold at which to intervene with bone-active drugs, the dose or duration of exposure to steroid therapy that warrants intervention, and the demonstration of the efficacy of fracture prevention for different bone-active drugs or for a combination of these drugs.

Biochemical markers of bone turnover that are specific to bone allow study of the subtle changes in bone turnover associated with osteoporosis. They have been evaluated in Paget's disease of the bone and chronic renal failure. This review focuses on the use of biochemical markers of bone turnover in osteoporosis. The data in this review period are numerous and varied due to the growing interest in the use of biochemical markers of bone turnover in clinical practice. The data provide support for the use of the newer bone turnover markers for monitoring treatment of osteoporosis, if care is taken to minimize sources of variability.

Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = -0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation.

To The Editor: We read with interest the paper, “Effect of Bisphosphonates on Periprosthetic Bone Mineral Density After Total Joint Arthroplasty. A Meta-Analysis” (2005;87:293-301), by Bhandari et al. We were intrigued by the findings that the effect size of bisphosphonate therapy was greater after procedures performed with cemented implants than after those performed with uncemented implants and greater after total knee arthroplasty than after total hip arthroplasty. We noted that both of the total knee arthroplasty studies involved cemented implants but that half of the total hip arthroplasty studies involved uncemented implants. Would the authors clarify whether cementation and joint site were independent predictors of drug efficacy, or whether the greater effect after procedures involving cemented implants might have been due to the common variable effect of total knee arthroplasty? The authors also stated that, in our study1, the effect of a single postoperative dose of pamidronate on femoral bone mineral density was lost at six months. We … Corresponding author: Mohit Bhandari, MD Department of Clinical Epidemiology and Biostatistics McMaster University Health Sciences Center Room 2C9 1200 Main Street West Hamilton, ON L8N 3Z5, Canada bhandam{at}mcmaster.ca

OBJECTIVE To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN AND PATIENTS Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2-3 years in 15 healthy women aged 45-54 years. Nine remained premenopausal and six became post-menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 post-menopausal women, aged 45-54 years, who were participating in a double-blind study. MEASUREMENTS Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion. RESULTS Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post-menopausal values were 30-50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean +/- SEM: urinary pyridinoline (premenopausal) = 29 +/- 2 vs urinary pyridinoline (post-menopausal) = 38 +/- 6, P < 0.05; urinary deoxypyridinoline (premenopausal) = 8 +/- 1 vs urinary deoxypyridinoline (post-menopausal) = 12 +/- 1, P < 0.05). Three months of post-menopausal hormone replacement therapy decreased (P < 0.001) both to premenopausal levels. CONCLUSION Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy.