Adynamic Bone Disease

Adynamic bone disease is low turnover renal osteodystrophy characterised by markedly reduced bone formation and resorption, few osteoblasts and osteoclasts, and no accumulation of unmineralised osteoid.

It is found in 20 to 40% of dialysis patients on bone biopsy and is now the commonest histological lesion in many centres.

Bone cannot buffer calcium or phosphate loads, so hypercalcaemia, vascular calcification and fractures follow.

Risk factors

• Over suppression of parathyroid hormone by calcium based binders, active vitamin D analogues, calcimimetics or parathyroidectomy.

• High dialysate calcium, peritoneal dialysis, diabetes, older age, malnutrition and inflammation, uraemic toxins, glucocorticoids, aluminium accumulation, bisphosphonates and denosumab.

Consequences

Fracture risk similar to or higher than that of high turnover disease, reduced skeletal calcium buffering with hypercalcaemia, extra-skeletal calcification and higher cardiovascular mortality.

• Often asymptomatic.
• Bone pain, fractures (hip, vertebrae, ribs), delayed fracture healing, proximal weakness.
• Hypercalcaemia after calcium or vitamin D exposure; vascular and valvular calcification; calciphylaxis.
• Hip and spine fractures in older diabetic patients on peritoneal dialysis.

Red flags

• Parathyroid hormone under 2 times the upper limit of normal with corrected calcium above 2.5 mmol/L.
• New fracture on dialysis, rapid progression of vascular calcification.
• Aluminium exposure with bone pain, myopathy and microcytic anaemia.

Biochemistry

• Parathyroid hormone under 2 times the upper limit of normal in dialysis (less than about 100 pg/mL), low or normal bone specific alkaline phosphatase, low normal or high calcium, normal or high phosphate. Biochemical thresholds have limited accuracy: values between 2 and 9 times the upper limit do not exclude low turnover.
• Aluminium level, 25-hydroxyvitamin D, glucose control (HbA1c), albumin.

Imaging. DXA shows low bone mineral density but cannot distinguish turnover. Radiographs and CT show vascular calcification.

Bone biopsy. Reference test: low or absent tetracycline label uptake, low bone formation rate, few cells, normal osteoid thickness. Indicated for unexplained fractures, hypercalcaemia, suspected aluminium and before antiresorptive therapy in G4 to G5D.

Differential diagnosis

• High turnover disease (high parathyroid hormone), osteomalacia (Looser zones, raised alkaline phosphatase, osteoid accumulation), age related and glucocorticoid osteoporosis, primary hyperparathyroidism, myeloma, aluminium toxicity.

First line: reduce suppression and the calcium load

• Stop or reduce calcium based binders (limit total elemental calcium to 1.5 g daily, or none if hypercalcaemic) and use sevelamer carbonate 800 mg three times daily with meals or lanthanum carbonate 500 mg with meals, titrated to phosphate 1.1 to 1.7 mmol/L.
• Withdraw or reduce active vitamin D (alfacalcidol, calcitriol, paricalcitol) and calcimimetics (cinacalcet 30 mg daily or lower, etelcalcetide) when parathyroid hormone is under 2 times the upper limit of normal or calcium is above 2.5 mmol/L. Allow parathyroid hormone to rise towards 2 to 9 times the upper limit.
• Dialysate calcium 1.25 mmol/L (1.0 mmol/L temporarily if hypercalcaemic with caution for intradialytic hypotension and arrhythmia). In peritoneal dialysis use a low calcium dialysate (1.25 mmol/L).

Address contributors

• Stop aluminium exposure (water treatment, aluminium containing binders); treat toxicity with deferoxamine 5 mg/kg intravenously once weekly during the last hour of dialysis for 2 to 3 months, repeating aluminium level 4 weeks after each course.
• Optimise glycaemic control, nutrition (protein 0.8 g/kg daily and adequate energy), acidosis (bicarbonate at least 22 mmol/L) and inflammation. Minimise glucocorticoids. Correct 25-hydroxyvitamin D to at least 50 nmol/L with cholecalciferol 800 to 2000 units daily.

Fracture risk

• Avoid bisphosphonates and denosumab (suppress remodelling further). Teriparatide 20 microg subcutaneously daily for up to 24 months has been used in selected patients with biopsy proven low turnover, under specialist supervision, with calcium checked within 1 week of starting.
• Falls prevention, weight bearing exercise, hip protectors for high risk older patients.

Monitoring. Calcium, phosphate and parathyroid hormone monthly to 3-monthly after changes; alkaline phosphatase 3-monthly. Repeat biopsy only if the decision depends on it.

Referral and escalation. Nephrology and metabolic bone specialist review for fractures, persistent hypercalcaemia or before any antiresorptive; bone biopsy at a specialist centre.

Special groups

• Peritoneal dialysis: use calcium 1.25 mmol/L dialysate and avoid calcium based binders.
• Diabetes: strict glycaemic control prevents progression.
• Transplant recipients: glucocorticoid sparing regimens and bone density monitoring.