Fractures in CKD: Screening and Management
Fractures in CKD: Screening and Management
Tetracycline double-labeled transiliac bone biopsy with histomorphometry is the gold standard to assess bone quality and strength, and uniquely bone turnover; note that all the other noninvasive measures give static assessments of bone turnover. Unfortunately, bone biopsy is not routinely performed, mainly because it is invasive, and requires specialized expertise, both to obtain the biopsy and interpret the histomorphometric findings. Further, bone biopsy is limited as it only gives information about bone at one point in time and from one site, and intersample variation should be taken in to account to assess the minimal difference required in order to affirm that changes noted in a repeat biopsy are significant.
That said, bone histomorphometry can provide information about the pathophysiology of bone loss in CKD that may, ultimately, increase our understanding of fracture risk in CKD. Specifically, bone histomorphometry can evaluate cortical bone compartments, this is highly relevant as previous noninvasive studies have shown a faster bone loss in the cortical area in CKD patients. For example, bone histomorphometry confirmed data from HR-pQCT, demonstrating that increased cortical porosity and erosion are present in dialysis patients with hyperparathyroidism and with a higher trabecular bone turnover. In pediatric CKD patients, similar findings were described. However, this difference was present primarily in external, not internal, cortical bone. The investigators also found a higher osteoid accumulation in the external cortical bone of children with hyperparathyroidism, suggesting that this site is the most active in terms of metabolism and response to parathyroid hormone (PTH). We recently measured cortical porosity in bone biopsies from dialysis patients who have been followed for one year. An increase in cortical porosity was observed, which was more pronounced in black patients and in those with high PTH. If confirmed by other studies, our findings show direct effects of CKD-MBD management on cortical bone, challenging the effects of conventional CKD-MBD therapy on the risk for fracture.
It is important to note that in contrast to DXA, there are no studies that report on the ability of bone histomorphometry to predict incident fractures in CKD. That said, bone histomorphometric studies have contributed substantially to our understanding of the pathophysiology of bone aberrations in CKD-MBD and, ultimately, this may increase our understanding of the pathophysiology of increased fracture risk in CKD. Future research should include a prospective study designed to compare and contrast DXA, HR-pQCT, and bone histomorphometry.
In the general population, management of osteoporosis involves both nonpharmacological, including changes in lifestyle and dietary habits, and pharmacological approaches in patients at high risk for fracture and presenting with an established osteoporosis. Guidelines recommend supplementation of calcium and vitamin D, as well as, inhibitors of bone resorption (bisphosphonates, denosumab, and selective estrogen receptor modulators), stimulators of bone formation (teriparatide, romosozumab) or chemical entities decreasing bone resorption and stimulating bone formation (strontium ranelate, available only in Europe and South America).
KDIGO guidelines recommend that osteoporosis management and treatment for patients with stages 1–3 CKD should be the same as for patients without CKD, as long as they do not present with features of CKD-MBD. For patients with later stages of CKD, a bone biopsy is required to accurately identify the type of bone disease prior to initiating treatment, keeping in mind that most FDA approved pharmacological choices for osteoporosis lack evidence for fracture reduction in advanced CKD (stages 4–5).
Bone Biopsy
Tetracycline double-labeled transiliac bone biopsy with histomorphometry is the gold standard to assess bone quality and strength, and uniquely bone turnover; note that all the other noninvasive measures give static assessments of bone turnover. Unfortunately, bone biopsy is not routinely performed, mainly because it is invasive, and requires specialized expertise, both to obtain the biopsy and interpret the histomorphometric findings. Further, bone biopsy is limited as it only gives information about bone at one point in time and from one site, and intersample variation should be taken in to account to assess the minimal difference required in order to affirm that changes noted in a repeat biopsy are significant.
That said, bone histomorphometry can provide information about the pathophysiology of bone loss in CKD that may, ultimately, increase our understanding of fracture risk in CKD. Specifically, bone histomorphometry can evaluate cortical bone compartments, this is highly relevant as previous noninvasive studies have shown a faster bone loss in the cortical area in CKD patients. For example, bone histomorphometry confirmed data from HR-pQCT, demonstrating that increased cortical porosity and erosion are present in dialysis patients with hyperparathyroidism and with a higher trabecular bone turnover. In pediatric CKD patients, similar findings were described. However, this difference was present primarily in external, not internal, cortical bone. The investigators also found a higher osteoid accumulation in the external cortical bone of children with hyperparathyroidism, suggesting that this site is the most active in terms of metabolism and response to parathyroid hormone (PTH). We recently measured cortical porosity in bone biopsies from dialysis patients who have been followed for one year. An increase in cortical porosity was observed, which was more pronounced in black patients and in those with high PTH. If confirmed by other studies, our findings show direct effects of CKD-MBD management on cortical bone, challenging the effects of conventional CKD-MBD therapy on the risk for fracture.
It is important to note that in contrast to DXA, there are no studies that report on the ability of bone histomorphometry to predict incident fractures in CKD. That said, bone histomorphometric studies have contributed substantially to our understanding of the pathophysiology of bone aberrations in CKD-MBD and, ultimately, this may increase our understanding of the pathophysiology of increased fracture risk in CKD. Future research should include a prospective study designed to compare and contrast DXA, HR-pQCT, and bone histomorphometry.
New Therapeutic Evidence
In the general population, management of osteoporosis involves both nonpharmacological, including changes in lifestyle and dietary habits, and pharmacological approaches in patients at high risk for fracture and presenting with an established osteoporosis. Guidelines recommend supplementation of calcium and vitamin D, as well as, inhibitors of bone resorption (bisphosphonates, denosumab, and selective estrogen receptor modulators), stimulators of bone formation (teriparatide, romosozumab) or chemical entities decreasing bone resorption and stimulating bone formation (strontium ranelate, available only in Europe and South America).
KDIGO guidelines recommend that osteoporosis management and treatment for patients with stages 1–3 CKD should be the same as for patients without CKD, as long as they do not present with features of CKD-MBD. For patients with later stages of CKD, a bone biopsy is required to accurately identify the type of bone disease prior to initiating treatment, keeping in mind that most FDA approved pharmacological choices for osteoporosis lack evidence for fracture reduction in advanced CKD (stages 4–5).
