Poster Presentation ANZBMS-MEPSA-ANZORS 2022

A 76 yo female was referred to metabolic bone clinic following a recent hospital admission for a L5 transverse spine and left ala of sacrum fracture after a fall from standing height. This was on the background of a history of osteoporosis diagnosed at age 60 for which she was managed on denosumab since 2019, with no history of missed or delayed dosing (last dose was administered in January 2022). Prior to this she was prescribed weekly alendronate. Her fracture history was significant for a previous right superior and inferior pubic rami fracture, sustained two months prior. Her other comorbidities include type 2 diabetes mellitus and hypertension. She has recently been diagnosed with end stage renal disease with an eGFR of 13 ml/min.

Her laboratory findings demonstrated stable renal function (urea 24.8 mmol/L, creatinine 289 umol/L, eGFR 13 ml/min/1.73m²), normal calcium (corrected calcium 2.55 mmol/L) and vitamin D (80 nmol/L) and slightly elevated phosphate (1.71 mmol/L). Other secondary screens included a slightly elevated parathyroid hormone (7.4 pmol/L) reflecting secondary hyperparathyroidism, normal thyroid function tests (TSH 4.37 mIU/L), negative coeliac and myeloma screens. Her crosslaps were 380 ng/L and ALP 84 U/L.

Her most recent CT of her lumbar spine demonstrated acute bilateral L5 transverse process and left sacral ala fractures as well as a subacute right sacral ala fracture. There were chronic T11, T12, L1, L2 and L4 vertebral body fractures present.

Results of her previous DEXA scans are as follows:

Despite improvements in her bone mineral density in both the spine and hip, Deidre has continued to sustain minimal trauma fractures thus raising the question of whether this represents failure of denosumab therapy and thus the potential role of anabolic agents such as teriparatide or romosozumab mindful of her history of end stage kidney disease.

Osteoporosis is characterised by impaired bone quality and quantity, resulting in increased risk of fracture. It can be difficult to diagnose in the setting of CKD and treatment options are limited when there is a co- existing CKD related mineral and bone disorder (CKD-MBD). This condition is characterised by alterations in calcium, phosphate, parathyroid and vitamin D metabolism, in addition to abnormalities in bone turnover and mineralisation. The gold standard of diagnosis is by an iliac crest bone biopsy, which occurs infrequently given the invasiveness of this procedure. Given this, the exclusion of CKD-MBD is difficult.

The treatment of osteoporosis is no different in stages 1 to 3 CKD compared to those with normal renal function. Those with moderate to severe CKD, this presents more of challenge. There are limited evidence-based guidelines on the management of osteoporosis in end stage renal disease who have continued to fracture despite previous bisphosphonate or denosumab therapy. Denosumab use in this cohort can be complicated by severe, symptomatic hypocalcaemia.

Anabolic agents such as teriparatide (recombinant peptide of human PTH) and more recently romosozumab, a monoclonal anti sclerostin antibody, have been increasing used in those who are deemed very high fracture risk and have continued to fracture despite being on antiresorptive therapy. Their role in end stage renal failure has been limited to either case reports or small observational retrospective or prospective studies. Post hoc analysis of the Fracture Prevention Trial demonstrated that teriparatide improved bone mineral density and was safe in patients with an eGFR as low as 30 ml/min/1.73m². A post marketing study in Japan of 1847 patients with osteoporosis and high fracture risk included those with stage 4 (n= 30) and 5 CKD (n =3). Bone mineral density increases were noted in those with stage 4 CKD and no adverse effects were observed in both groups⁴. Teriparatide may be beneficial in those with adynamic bone disease however this is based on data obtained in published case reports5.

There has been retrospective data showing romosozumab use in those with mild to moderate renal impairment (eGFR 30-60 ml/min/1.73m²) reduced the risk of new vertebral fractures². There is limited data available on the use of romosozumab in more severe kidney disease (eGFR < 30 ml/min/1.73m²) for fracture prevention².  Romosozumab in a cohort of patients on haemodialysis demonstrated improvements in bone mineral density with increases in bone formation markers with no symptomatic hypocalcaemia and lower cardiovascular events compared with the untreated group6. 

Both osteoporosis and CKD are common conditions that are increasing in prevalence given the current ageing population. With increasing severity of CKD, treatment choices are complex and difficult which is compounded by a paucity of trial data.

• The management of osteoporosis in end stage renal disease is complex especially in the setting of chronic kidney disease related bone mineral disorder.
• The risk of fragility fractures and associated fracture related mortality is high
• The role of anabolic agents such as teriparatide and romosozumab in end stage renal disease is limited to small cohort studies which have demonstrated favourable effects however further studies are required