In a recent survey of 630 bone biopsy samples from patients with CKD stage 5 on dialysis, bone turnover was low in 52%, normal in 21% and high in 27% of biopsies. Defective mineralization was found in only 3%. Since the introduction of vitamin D analogs, the dominant bone disease phenotype in dialysis patients has remarkably changed. Now, adynamic bone disease is the primary bone abnormality. Since we are continuously trying to balance vit. D dose/PTH levels, I was interested in the question: if I have to choose, should I error in the side of higher or lower PTH?
I learned some interesting points about bone metabolism that I would like to share with you. When assessing bone volume abnormalities, it is important to differentiate between cortical and cancellous bone. The cortical bone, as the name implies, forms the cortex (outer shell) of most bones, being harder, stiffer and stronger than cancellous bone. It is responsible mainly for the mechanical function of the bones. On the other hand, the cancellous bone typically occurs at the ends of long bones, it has many trabeculations and is highly vascularized. Due to its high surface area, it is the predominant place of metabolic activity of the bone (e.g. exchange of calcium ions).
Now comes the interesting part. Loss of cortical bone occurs mainly in patients with high turnover bone disease, while loss of cancellous bone is often seen in patients with low bone turnover. The clinical outcome of decreased bone strength is fracture, while abnormal metabolic activity results in the inability to maintain mineral homeostasis, which is associated with vascular and soft tissue calcifications. Following these lines, adynamic bone is typically asymptomatic but it is strongly associated with hypercalcemia, cardiovascular calcifications and mortality.
What are the risk factors for adynamic bone disease?
High calcium load, low PTH and vitamin D over-treatment. Older patients, DM and peritoneal dialysis are additional associated factors.
Can we predict the type of bone disease in a dyalisis patient with PTH levels?
No, but it could give you some direction:
- Intact serum PTH values below 100 pg/mL are associated with a decreased likelihood of osteitis fibrosa and an increased incidence of adynamic bone disease.
- An intact serum PTH level above 450 pg/mL is typically associated with hyperparathyroid bone disease and/or mixed uremic osteodystrophy.
- Intermediate PTH levels between 100 and 450 pg/mL may be associated with normal, elevated bone remodeling, or even reduced bone remodeling.
Bone specific alkaline phosphatase levels could also be an adjunctive marker (below 7 ng/mL low bone turnover, above 20 high bone turnover). Radiographic examination of bone can provide important information regarding the presence of hyperparathyroidism (such as subperiosteal resorption). However, radiographic findings are less sensitive than PTH levels and will not establish the type of bone disease. The gold standard is bone bx.
When should you perform a bone bx?
Controversial topic but a bx could be considered in the setting of unexplained fractures, unexplained hypercalcemia, and/or unexplained hypophosphatemia; persistent bone pain; possible aluminum toxicity; and before therapy with bisphosphonates.
How should adynamic bone be treated?
Lower PTH levels should be treated by decreasing the doses of calcium-based phosphate binders, vitamin D, a low dialysate calcium concentration, and perhaps by the use of non-calcium-based phosphate binders (though no data yet supporting this).
My feeling is that we should be cautious in the administration of vitamin D and adjust with small increments based on PTH levels, especially due to the metabolic complications of adynamic bone and difficulty to reverse it. Adynamic bone disease is a relative new entity and long-term complications have not been fully determined yet. I must confess that since PTH does not truly predict the type of bone disease, it is a hell of an empirical area…
I added the link on the blog now. It just came out on J Bone Miner Res. 2010 Dec 2.
– Renal osteodystrophy in the first decade of the new millennium-analysis of 630 bone biopsies in black and white patients.
Malluche HH, Mawad HW, Monier-Faugere MC.
Can you pls quote the reference of "In a recent survey of 544 bone biopsy samples from patients with CKD stage 5 on dialysis, bone turnover was low in 52%, normal in 21% and high in 27% of biopsies. Defective mineralization was found in only 3%where"
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Dear Dr Topf, thanks for your comments. There was a typo regarding the PTH levels as you pointed out. I will correct it.
Regarding the DCOR trial, I agree that it doesn't deal directly with bone outcomes, but it seems the metabolism of Ca/PO4 in bone disease and its cardiovascular consequences is of great importance and due to to small space in the blog I couldn't explore that further… I changed the hyperlink to another trial that specifically deals with bone disease and non-calcium based regimen. Thanks for your feedback!
You wrote "How should adynamic bone be treated?
Lower PTH levels should be achieved by…"
did you mean "Lower PTH levels should be TREATED by…"
Also referring to the DCOR trial when referring to adjusting PTH levels by choosing a binder is misrepresenting what the DCOR trial was trying to show. Strangely this study on one of the principle drugs for secondary hyperparathyroidism had little to do with bone disease, as the only outcomes assessed were hospitalizations, mortality and morbidity and medicare expenditures.