Oral Presentation ANZBMS-MEPSA-ANZORS 2022

We present a case of a 46-year-old male who underwent a bilateral single sequential lung transplant (BSSLTX) for severe COVID pneumonitis complicated by multiple vertebral fractures and evidence of bony demineralisation.

 

His background was significant for type-2 diabetes treated with insulin and Empagliflozin; previous lumbar surgery; and an unprovoked deep vein thrombosis.  He was a non-smoker and did not consume alcohol.  There was no previous history of fracture, nor a family history of osteoporosis. At the time of infection, he had received 2 doses of COVID vaccination.

 

He presented to hospital with respiratory distress and tested positive for COVID-19 on admission. Despite treatment with a dexamethasone, remdesivir and tocilizumab he was intubated for hypoxic respiratory failure and was commenced on venous-venous extracorporeal membrane oxygenation.

 

He received a BSSLTX on day 68 of his admission. Post-transplantation, his course was complicated by critical illness neuropathy, anuric renal failure requiring dialysis, worsening type 2 respiratory failure, left pleural effusion requiring drainage, fluid overload and right sided phrenic nerve palsy requiring re-intubation for worsening respiratory distress.

 

A CT of his chest/abdomen/pelvis demonstrated bony demineralisation as well as new compression fractures of the T7 endplate with 25% height loss, T8 vertebral body with 20% loss of height and reduced height of the T9 and T11 superior and inferior endplates. A subsequent CT two weeks later showed progressive height loss of multiple thoracic and lumbar vertebral bodies as well as generalised increased density of both femoral heads suspicious for the development of osteonecrosis.

 

 

 

 

Figure 1; CT chest/abdomen/pelvis demonstrating generalised bony demineralisation, compression fracture of T7 and T8 vertebra

 

 

Figure 2; repeat CT demonstrating progressive height loss of multiple thoracic and lumbar vertebral bodies

 

His biochemistry demonstrated an eGFR of 22 ml/min/1.73m2 and creatinine of 297 umol/L.  Corrected calcium was initially normal but became elevated to a peak of 3.17 mmol/L (2.10-2.60) with PTH of 1.5 pmol/L (2.0-9.0), phosphate 0.76 mmol/L (0.70-1.50) and magnesium 0.80 mmol/L (0.70-1.10). Bone turnover markers were elevated with CTX 2010 ng/L (100-600), P1NP 635 ug/L (18-80) and bone-specific ALP 45.1 ug/l (4.4-24.6). His 25-OH vitamin D was normal on replacement at 99 nmol/L. TSH was 1.67 mU/L. His myeloma screen was negative and there was no evidence of malignancy CT imaging.

 

A bone densitometry was unable to be performed due to immobility requiring hoist transfer. He was managed with a dose of renally-adjusted Zoledronic acid 2 mg with normalisation of his hypercalcaemia by day 3.

 

Unfortunately he had ongoing worsening type 2 respiratory failure and renal failure and succumbed to his illness after haemodialysis was ceased.

 

 

Discussion

Vertebral fractures (VFs) have been shown to be common in patients admitted with COVID19, and are associated with increased requirement for non-invasive ventilation and poorer respiratory outcomes including decreased pulmonary vital capacity, restrictive pulmonary dysfunction, and increased mortality.[i]

 

Our case had evidence of rapid and progressive bone loss resulting in multiple vertebral fractures. The bone loss was likely contributed to by immobility and bone unloading. In rodent models of immobility, changes in bone markers occur within 15-21 days.[ii]  Bed rest alone in humans has been shown to result in significant early spinal bone density loss of 3.6% at 27 days. Reambulation resulted in restoration of lumbar spine mineral content by 4 months.[iii] Patients with spinal cord injuries have lower limb bone mineral density decreases of 4% per month below the level of the injury.[v]

 

Apart from immobility, other possible contributors to bone loss in this case may include the release of inflammatory cytokines such as IL6, TNFa, IL1 and IL2 resulting in osteoclastogenesis, high-dose corticosteroid use, acidaemia, and hypoxia.[vi]

 

Prolonged ventilation in itself has been hypothesised to lead to injury of the lung leading to the release of inflammatory agents including TLR4, NOD like receptor P3 and IL1, in turn accelerating bone resorption via accelerated osteoclastogenesis via RANKL.[vi]

 

Additionally, vertebral fractures may also exacerbate respiratory function with evidence that vertebral fractures result in reduced forced vital capacity (FVC) and vital capacity, which may suggest a complex bidirectional interaction between respiratory dysfunction and bone status.[vii]

 

Conclusions

 

We highlight a case of severe COVID infection requiring lung transplantation resulting in significant bony demineralisation and multiple vertebral compression fractures. Patients with acute critical illness demonstrate early rapid bone demineralisation with an associated increase in fracture risk. Patients with severe COVID-19 have been shown to have a high prevalence of thoracic vertebral fractures with consequences including possible influences on respiratory function. Early detection and management of fractures may prevent subsequent fractures and improve respiratory status in patients with COVID and other respiratory distress syndromes.

 

[i] di Filippo L, Formenti AM, Doga M, Pedone E, Rovere-Querini P, Giustina A. Radiological Thoracic Vertebral Fractures are Highly Prevalent in COVID-19 and Predict Disease Outcomes. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e602-e614. doi: 10.1210/clinem/dgaa738. PMID: 33159451; PMCID: PMC7797741.

 

[ii] Zhang B, Cory E, Bhattacharya R, Sah R, Hargens AR. Fifteen days of microgravity causes growth in calvaria of mice. Bone. 2013 Oct;56(2):290-5. doi: 10.1016/j.bone.2013.06.009. Epub 2013 Jun 20. PMID: 23791778; PMCID: PMC4110898.

 

[iii] Krølner B, Toft B. Vertebral bone loss: an unheeded side effect of therapeutic bed rest. Clin Sci (Lond). 1983 May;64(5):537-40. doi: 10.1042/cs0640537. PMID: 6831837

 

[iv] Martin CT, Niewoehner CB, Burmeister LA. Significant Loss of Areal Bone Mineral Density Following Prolonged Bed Rest During Treatment With Teriparatide. J Endocr Soc. 2017 Apr 24;1(6):609-614. doi: 10.1210/js.2017-00049. PMID: 29264514; PMCID: PMC5686584.

 

[v] Martin CT, Niewoehner CB, Burmeister LA. Significant Loss of Areal Bone Mineral Density Following Prolonged Bed Rest During Treatment With Teriparatide. J Endocr Soc. 2017 Apr 24;1(6):609-614. doi: 10.1210/js.2017-00049. PMID: 29264514; PMCID: PMC5686584

 

[vi] Watanabe R, Shiraki M, Saito M, Okazaki R, Inoue D. Restrictive pulmonary dysfunction is associated with vertebral fractures and bone loss in elderly postmenopausal women. Osteoporos Int. 2018 Mar;29(3):625-633. doi: 10.1007/s00198-017-4337-0. Epub 2017 Dec 7. PMID: 29218382.

 

[vii] Gugala Z, Cacciani N, Klein GL, Larsson L. Acute and severe trabecular bone loss in a rat model of critical illness myopathy. J Orthop Res. 2021 Aug 11. doi: 10.1002/jor.25161. Epub ahead of print. PMID: 34379332.