Introduction
Chronic kidney disease – mineral bone disorder (CKD-MBD) is an early manifestation of renal insufficiency which progresses with advancing chronic kidney disease (CKD) stage. Reduced phosphate filtration by declining nephron mass increases osteocyte production of fibroblast growth factor (FGF)-23, which in turn suppresses hydroxylation of 25(OH) vitamin D by the kidney and reducing intestinal calcium absorption. This in turn leads to parathyroid hypertrophy and unregulated parathyroid hormone (PTH) secretion.(1) Secondary hyperparathyroidism subsequently develops as an adaptive response to this calcium-phosphate imbalance and is commonly associated with hyperdynamic bone disease, but a variety of osteodystrophies may occur in the setting of CKD-MBD, including osteomalacia, osteoporosis, and adynamic bone disease. Intact and whole PTH measurement may not reliably distinguish between bone turnover states.(2) Bone biopsy series have suggested adynamic bone disease to be the most frequent lesion overall,(3) although hyperdynamic bone disease appears to predominate in patients of Black African ancestry.(3) Mortality, mainly arising from cardiovascular events and increased fracture risk are the most feared complications of CKD-MBD.(2) Risk of hip fractures is significantly increased in CKD.(2) The prevalence of clinically significant vertebral fractures in CKD-MBD is poorly documented. Symptomatic neurological deficit arising from vertebral CKD-MBD is commensurably rare and typically involves the cervical spine.(4) We report an unusual case of thoracolumbar hyperdynamic CKD-MBD arising from secondary hyperparathyroidism presenting as acute paraplegia.
Case report
A 58-year-old female, on thrice-weekly in-centre haemodialysis for 8 years, presented with bilateral lower limb weakness. The patient reported lower backache for the antecedent 2 months. Neurological examination localised the pathology to the lower thoracic spinal cord and conus medullaris, with asymmetric flaccid paraparesis (2–3/5 power) and decreased anal tone. The deep tendon reflexes were absent at the knees, but present at the ankles with downgoing plantar reflexes. There was a sensory level to pinprick from T12 downwards with mild truncal weakness. Salient laboratory data at presentation is presented in Table 1.
Salient laboratory data at presentation | ||
---|---|---|
At presentation | Laboratory normal | |
Creatinine (µmol/L) | 447 | 49–90 |
eGFR (mL/min/1.73 m2) | 9 | >60 |
Corrected calcium (mmol/L) | 2.39 | 2.20–2.55 |
Magnesium (mmol/L) | 0.85 | 0.63–1.05 |
Phosphate (mmol/L) | 1.92 | 0.72–1.42 |
Alkaline phosphatase (IU/L) | 163 | 42–98 |
Parathyroid hormone (pmol/L) | 88.2 | 1.60–6.0 |
Vitamin B12 (pmol/L) | 458 | 156–673 |
The plain radiograph of the lumbar spine revealed changes suggestive of rugger jersey spine and early degenerative changes. Initial computerized tomogram of the spine showed mixed lytic and sclerotic lesions throughout the axial and appendicular skeleton with loss of vertebral height of T12. Subsequent magnetic resonance imaging (MRI) spine revealed marginal dense sclerosis alternating with parallel lucent bands especially pronounced in the thoracolumbar vertebrae – the so-called “rugger-jersey spine” of secondary hyperparathyroidism (Figure 1). An anterior wedge compression fracture of the T12 vertebral body with posterior bulging of the T11/T12 intervertebral disc was observed, resulting in spinal cord oedema as evidenced by T2-hyperintensity in the adjacent spinal cord (Figure 1, arrow), as well as nerve root impingement of bilateral T12 descending nerve roots in the spinal canal and bilateral T11 exiting nerve roots in the neural foramina.
Review of the patient's antecedent laboratory data showed acceptable calcium (median 2.30 mmol/L, interquartile range 2.23–2.42 mmol/L) and phosphate levels (median 1.65 mmol/L, interquartile range 1.43–1.86 mmol/L) but poor control of PTH (median 107 pmol/L, interquartile range 87–139 pmol/L) despite active prescription of alfacalcidol vitamin D analogue and calcium carbonate. The patient reported intermittent compliance with prescribed dosing, accounting for the significant variability in measured PTH observed. The calcium, phosphate and PTH levels preceding presentation are presented in Figure 2.
Nerve conduction studies, electromyography and cerebrospinal fluid analysis failed to identify pathology other than that indicated on MRI. Screening for malignancy with vertebral metastases as a differential for the reported lytic lesions was negative.
The patient was referred for consideration for surgical intervention, but in view of the extensive bony disease and comorbidities, decompression was deferred. A course of dexamathasone was prescribed for the spinal cord oedema. Compliance with prescribed medication and phosphate dietary restriction was emphasized and the patient was referred for physiotherapy. Subsequent follow-up demonstrated stabilization of CKD-MBD laboratory parameters within Chronic Kidney Disease Improving Global Outcomes (KDIGO) targets and the patient has regained limited independent mobility.
Discussion
This case illustrates a rare but clinically significant complication of uncontrolled secondary hyperparathyroidism in patients with ESKD.
The “rugger-jersey spine”, comprising sclerotic bands along vertebral body endplates with central body areas of lucency, said to resemble the stripes of a rugby sweater, is a well-established radiological feature of hyperdynamic CKD-MBD.(5) In untreated secondary hyperparathyroidism, increased PTH-mediated osteoclastic activity results in bone resorption. Subsequent osteoblast activation in the setting of poor calcium availability results in the deposition of hydroxyapatite-deficient osteoid which is radiopaque, giving rise to the eponymous alternating bands.(5) Excessive osteoclastic resorption may lead to the development of a Brown tumour (osteoclastoma), a cavity in bone in which fibrous tissue undergoing liquefaction and necrosis progressively accumulates.(6) Although Brown tumours typically affect the pelvis, ribs, femora, and facial bones, vertebral involvement has been described.(6) The radiological differential diagnosis for the sclerotic and lucent/lytic changes seen on spinal imaging includes metastatic disease or Paget's disease of bone.(5)Neurological compromise from vertebral CKD-MBD may occur as a result of fracture, destructive spondyloarthropathy, compression by Brown tumour expansion or amyloid deposition within the intervertebral disc. Despite the frequency of radiological changes, actual neurological deficit is rare. A review of published reports of significant neurological deficit due to CKD-MBD spondyloarthropathy found only 138 cases.(4) Forty-four percent of cases in this series presented with myelopathy and non-cervical spine involvement was rare.(4)Surgical treatment of spinal CKD-MBD presents unique challenges. In particular, associated osteoporosis increases the risk of hardware failure should internal fixation be required.(4) This, combined with the probability of disease progression, results in the likelihood of repeat revision surgery to be as high as 22%–40%.(4)
Control of PTH is required to prevent disease progression and to improve surgical response. Thus, medical therapy to achieve KDIGO targets is an essential component of treatment.(2) Vitamin D receptor analogues (VDRAs) are frequently prescribed to suppress PTH oversecretion.(1) Alfacalcidol (1 alpha-Hydroxyvitamin D3) is the only VDRA available in public health centres in South Africa. Use of this formulation in treating secondary hyperparathyroidism may be limited by a propensity to increase intestinal calcium and phosphate absorption, thus precipitating calciphylaxis.(1) Alternative vitamin D3 (maxacalcitol and falecalcitriol) and D2 (paricalcitol and doxercalciferol) VDRAs which produce less phosphataemia are not widely available in South Africa. The use of calcium-based phosphate binders is also subject to the risk of precipitating metastatic calcification through increased calcaemia; substitution with non-calcium phosphate binders such as sevelamer hydrochloride, lanthanum carbonate, or ferric citrate may be required in these cases.(1) The use of these non-calcium phosphate binders may also offer additional advantageous roles in directly suppressing PTH secretion and reversing parathyroid gland hypertrophy.
VDRA effects on serum calcium and phosphate levels may be obviated, through the use of calcimimetics (cinacalcet, etelcalcetide, and evocalcet), which bind to the calcium sensing receptor of parathyroid cells to inhibit PTH secretion and gland hypertrophy.(1) Combination therapy with calcimimetic and VDRA allows for lower dose of VDRA to prevent side-effects of increased calcaemia and metastatic calcification with increased risk of cardiovascular events.(2) The KDIGO guidelines recommend resorting to parathyroidectomy in those patients who fail to respond to first-line medical therapy.(2)
The presentation of our patient with significant symptomatic neurological deficit in the form of acute onset paraplegia constitutes a rare manifestation of secondary hyperparathyroidism in CKD, occurring on a background of chronic failure to control PTH levels brought about by poor adherence to prescribed VRDA and phosphate binders. Fortunately, counselling on pharmacological compliance and non-invasive treatment with physiotherapy and dexamethasone have resulted in sustained improvement and return to a degree of independent mobility.
Conclusion
Although secondary hyperparathyroidism and hyperdynamic CKD-MBD are common in the setting of CKD, neurological sequalae from vertebral involvement remain fortuitously rare. Treatment according to KDIGO guidelines may prevent and ameliorate this complication, obviating the need for surgery which carries with it a significant failure rate. Counselling patients on adherence to prescribed therapies is vital to prevent progression of CKD-MBD.