Disrupted bone metabolism in long-term bedridden patients

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SCIENCE
Disrupted bone metabolism in long-term bedridden patients
Key Take-Away: 

The study indicates that bone formation and resorption are accelerated in patients with <30 years of bed confinement, followed by a decrease in accreted bone metabolites. Thus, an appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

For preserving bone mass, mechanical tension is crucial. However, immovability for a long period of time causes bone atrophy and osteoporosis. Fractures are very common in children and adults with severe immotility who are confined to bed for long periods due to neuromuscular diseases, such as cerebral palsy, epilepsy, and encephalitis.

ABSTRACT: 
Background: 

For preserving bone mass, mechanical tension is crucial. However, immovability for a long period of time causes bone atrophy and osteoporosis. Fractures are very common in children and adults with severe immotility who are confined to bed for long periods due to neuromuscular diseases, such as cerebral palsy, epilepsy, and encephalitis.

Low bone mineral density (BMD) and abnormal bone metabolism have been reported in immobilized patients. However, the available evidence showing long-term changes in BMD and bone metabolism has been limited. The expectation of life of patients with severe neuromuscular diseases has increased due to improvements in medical treatment and care. As a result, painful bone fractures remain one of the most serious complications of being bedridden, and the importance of maintaining bone health is increasing.

Rationale behind research

  • The available evidence showing long term changes in BMD and bone metabolism has been limited.

  • Therefore, this study was conducted to determine how long term-bed confinement affects bone metabolism.

Objective

To investigate how bed confinement for a prolonged period affects bone metabolism in patients with severe motor and intellectual disabilities, none of whom have stood or walked in their life.

Methods: 

  • Study outcomes

  • Bone mineral density: The BMD of lumbar spine 2–4 in the anteroposterior projection was assessed using dual energy X-ray absorptiometry (DXA). Radiologists checked for spinal deformities via the radiography of the lumbar spine and then used the frontal view of lumbar spine 2–4 to provide an accurate evaluation of BMD.

  • Bone metabolism assessment: For the assessment of bone metabolism, the levels of serum osteocalcin, urine N-terminal telopeptide (NTX), serum 25-hydroxy vitamin D (25(OH) vitamin D), serum intact parathyroid hormone (PTH), serum calcium, serum phosphorus, and serum alkaline phosphatase were measured. For evaluation of BMD levels, cutoff value (0.708 g/cm3) proposed for osteoporosis based on the guidelines for osteoporosis by the Japan Osteoporosis Society, Japanese Society for Bone and Mineral Research, and Japanese Osteoporosis Foundation was used. For the evaluation of osteocalcin and NTX levels, the cutoff values (4.5 ng/mL for osteocalcin and 54.3 nM BCE/mM Cr for NTX) proposed for predicting fracture based on the guidelines were used.

Results: 

Total 36 patient were enrolled.

Baseline: There was no significant differences in the baseline clinical characterstics among the causes of bedrest.

Outcomes

  • In 24 patients (67%), BMD levels were reduced below the cutoff value for osteoporosis (0.708 g/cm3) based on the Japanese guidelines for osteoporosis. There was no difference in the BMD levels among the causes of bedrest. The serum osteocalcin levels were greater than the cutoff value for predicting fracture (4.5 ng/mL) based on the guidelines in 30 of 36 patients (83%), and urine NTX levels were greater than the cutoff value for predicting fracture (54.3 nM BCE/mM Cr) in 28 patients (78%).

  • Among the bone metabolism markers, serum osteocalcin and urine NTX levels were negatively correlated with a bedridden period.

  • During the follow-up period, osteocalcin levels had decreased, but the number of patients with osteocalcin levels greater than the cutoff value for osteoporosis was still high.

  • The urine NTX levels tended to decrease, and the number of patients with BMD values less than the cutoff had decreased (17 patients [100%] in 1999; 12 patients [71%] in 2011). Among other bone metabolism markers, the 25(OH) vitamin D levels had increased, and the parathyroid hormone and phosphorus levels had decreased during the follow-up.

  • The urine NTX, phosphorus, and alkaline phosphatase levels in 1999 were negatively associated with the BMD levels in 2011. The parathyroid hormone levels in 1999 tended to be associated with the BMD levels in 2011. However, the osteocalcin levels in 1999 were not associated with the BMD levels in 2011. 

Conclusion: 

The results of the study indicates that patients who had been bedridden from birth exhibited low BMD and abnormal bone metabolism. In previous crosssectional studies, severe motor impairment, less physical activity, low nutritional status, and low calcium intake are all correlated with low BMD. In contrast, serum calcium, alkaline phosphatase, osteocalcin, and 25(OH) vitamin D are not correlated with BMD.

The role of anticonvulsants in low BMD is controversial, and in this study, the use of anticonvulsants was not associated with BMD. Here, high NTX levels at baseline were associated with reduced BMD during a follow-up period of 12 years in patients of 18 to 30 years. However, NTX was not correlated with BMD in patients with cerebral palsy aged <19 years in a previous cross-sectional study. Taken together, increased bone resorption seems to have an important role in osteopenia in patients who had been bedridden for a very long period from birth due to severe immobility. NTX, phosphorus, and alkaline phosphate may be useful in predicting the development of osteoporosis in the future.

Plos One
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