Bone Quality in Chronic Kidney Disease Patients: Current Concepts and Future Directions – Part II

Background: Patients with chronic kidney disease (CKD) have an increased risk of osteoporotic fractures, which is due not only to low bone volume and mass but also poor microarchitecture and tissue quality. The pharmacological and nonpharmacological interventions detailed, herein, are potential approaches to improve bone health in CKD patients. Various medications build up bone mass but also affect bone tissue quality. Antiresorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the ability to repair bone microdamage and cause an increase in bone brittleness. On the other hand, some osteoporosis therapies may cause a redistribution of bone structure that may improve bone strength without noticeable effect on BMD. This may explain why some drugs can affect fracture risk disproportionately to changes in BMD. Summary: An accurate detection of the underlying bone abnormalities in CKD patients, including bone quantity and quality abnormalities, helps in institution of appropriate management strategies. Here in this part II, we are focusing on advancements in bone therapeutics that are anticipated to improve bone health and decrease mortality in CKD patients. Key Messages: Therapeutic interventions to improve bone health can potentially advance life span. Emphasis should be given to the impact of various therapeutic interventions on bone quality

Bone Quality in CKD Patients: Current Concepts and Future Directions – Part I

Background: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures independently of BMD in CKD patients. Bone quality and fracture risk in CKD patients can be better assessed by utilizing new technologies such as trabecular bone score and high-resolution imaging studies. Additionally, invasive assessments such as bone histology and micro-indentation are useful counterparts in the evaluation of bone quality. Summary: A precise diagnosis of the underlying skeletal abnormalities in CKD patients is crucial to prevent further bone loss and fractures. We must consider bone quantity and quality abnormalities for management of CKD patients. Here in this part I, we are focusing on advances in bone quality diagnostics that are expected to help in proper understanding of the bone health in CKD patients. Key Messages: Assessment of bone quality and quantity in CKD patients is essential. Both noninvasive and invasive techniques for the assessment of bone quality are available

Bone Quality and Fractures in Women with Osteoporosis Treated with Bisphosphonates for 1 to 14 Years

Oral bisphosphonates are the primary medication for osteoporosis, but concerns exist regarding potential bone-quality changes or low-energy fractures. This cross-sectional study used artificial intelligence methods to analyze relationships among bisphosphonate treatment duration, a wide variety of bone-quality parameters, and low-energy fractures. Fourier transform infrared spectroscopy and histomorphometry quantified bone-quality parameters in 67 osteoporotic women treated with oral bisphosphonates for 1 to 14 years. Artificial intelligence methods established two models relating bisphosphonate treatment duration to bone-quality changes and to low-energy clinical fractures. The model relating bisphosphonate treatment duration to bone quality demonstrated optimal performance when treatment durations of 1 to 8 years were separated from treatment durations of 9 to 14 years. This may be due to a change in relationship of bone-quality parameters with treatment duration. This model also showed that the effects of bisphosphonate treatment duration were most highly correlated with changes in means and standard deviations of infrared spectroscopically derived mineral and matrix parameters and histomorphometric bone turnover parameters. A second model related treatment duration to bone fracture in all 22 patients who fractured while on treatment with bisphosphonates for more than 8 years. This second model showed that bisphosphonate treatment duration, not hip bone mineral density (BMD), was the most strongly correlated parameter to these low-energy bone fractures. Application of artificial intelligence enabled analysis of large quantities of structural, cellular, mineral, and matrix bone-quality parameters to determine relationships with long-term oral bisphosphonate treatment and fracture. Infrared spectroscopy provides clinically relevant bone-quality information of which bone mineral purity is among the most relevant. Nine or more years of bisphosphonate treatment was associated with abnormal bone mineral purity, matrix abnormalities, and low-energy fractures. These data justify limiting bisphosphonate treatment duration to 8 years

Effects of Treatment of Renal Osteodystrophy on Bone Histology

Renal osteodystrophy is characterized by abnormalities in bone turnover, mineralization, and bone volume. The effects of treatment modalities for renal osteodystrophy on bone should be analyzed with respect to these abnormalities. The major treatment modalities for renal osteodystrophy include phosphate binders, vitamin D compounds, and calcimimetics. Aluminum-containing phosphate binders have been shown to be toxic to bone secondary to their effects on bone turnover, mineralization, and bone volume. The use of calcium-based phosphate binders has been associated with the development of adynamic bone disease (low bone turnover), bone loss, and worsening of vascular calcifications. New nonaluminum, noncalcium phosphate binders have been developed (sevelamer hydrochloride and lanthanum carbonate). These agents show a potential for improvement in bone turnover and bone volume. Patients with renal osteodystrophy are deficient in calcitriol and often in calcidiol. Calcidiol deficiency has been underappreciated and deserves to be addressed in the treatment of patients with renal osteodystrophy. Calcitriol replacement therapy by daily oral administration is associated with frequent episodes of hypercalcemia and suppression of bone turnover in patients with stages 3 to 5 chronic kidney disease. Pulse oral or intravenous calcitriol administration induces frequent episodes of hypercalcemia or hyperphosphatemia, respectively, and achieves the same degree of correction of bone abnormalities. There are no data on the effects of paricalcitol or doxercalciferol on human bone. Experimental data, however, show that these two analogues and maxacalcitol may control serum parathyroid hormone levels without suppressing bone turnover. Calcimimetics lower parathyroid hormone levels and bone turnover

Prevalence of low bone formation in untreated patients with osteoporosis

Background Osteoporosis treatment usually starts with an antiresorber and switches to an anabolic agent if it fails. It is known that suppressing bone resorption also results in reduced bone formation. In addition, patients with prior treatment with antiresorbers may have reduced response to subsequent anabolic treatment. This study determined the prevalence of low bone formation in untreated osteoporosis patients to identify patients who may not be optimally treated under the current paradigm. Methods This is a cross-sectional study of bone samples stored in the Kentucky Bone Registry. Included samples were from adult patients presenting for workup of osteoporosis. Exclusion criteria were other diseases or treatments affecting bone. Patients underwent iliac crest bone biopsies after tetracycline labeling for identification of bone formation. Results 107 patients met study criteria, 92 White and 5 Black women and 10 White men. Forty percent of patients (43/107) had low bone formation/bone surface (BFR/BS Conclusions Starting treatment of osteoporotic patients with an antiresorber in all patients appears not optimal for a significant portion