Chronic heavy alcohol consumption impairs the ability of demineralized allogenic bone matrix to support osteoinduction in alcohol-naïve rats
Does alcohol consumption affect the success of bone grafts, and if so, how? This research bridges a critical knowledge gap by demonstrating that alcohol not only affects the recipient's healing process but can fundamentally compromise the quality of donor bone material itself, creating a dual mechanism that impairs healing.
College of Health researcher(s)
Highlights
Alcohol consumption by donors impairs graft quality
- Bone matrix from alcohol-consuming donors showed 45% lower IGF-1 levels
- This resulted in 23% lower bone volume when implanted in non-drinking recipients
- Finding suggests alcohol fundamentally alters bone matrix composition
Combined alcohol exposure creates worse outcomes
- The poorest healing occurred when both donor and recipient consumed alcohol
- This reveals a compounding negative effect on bone graft success
PTH treatment shows promise as a countermeasure
- Intermittent parathyroid hormone treatment improved healing of grafts
- Importantly, PTH worked with both normal and alcohol-exposed bone grafts
Abstract
Allografts play an important role in treatment of complex bone fractures and deformities. The purpose of this study was to test the hypothesis that alcohol consumption impairs graft incorporation and bone healing by two mechanisms: (1) by lowering osteoinductive capacity and (2) by suppressing bone formation.
We performed experiments using a demineralized allogeneic bone matrix (DBM) model in which DBM harvested from donor rats fed control or ethanol diet was implanted subcutaneously into recipient rats fed control or ethanol diet. We also evaluated the efficacy of intermittent parathyroid hormone (PTH) on bone graft incorporation (DBM from donor rats fed alcohol or control diet) using a critical size defect model. Bone formed during osteoinduction was measured by micro-computed tomography.
Experiment 1: Bone volume was lower in DBM harvested from ethanol-consuming donors 6 weeks following implantation into recipients fed control diet, indicating that exposure of the donor rats to ethanol lowered osteoinductive capacity.
Experiment 2: Bone volume was lower in DBM harvested 3 weeks following implantation from ethanol-consuming donors into ethanol-consuming recipients compared to DBM harvested from control donors implanted into control recipients or DBM harvested from control donors implanted into ethanol-consuming recipients.
Experiment 3: Ethanol consumption by donors resulted in a tendency for lower DBM bone volume (p = 0.085) whereas PTH treatment resulted in higher DBM bone volume in the critical size defect model. Our results suggest that chronic heavy alcohol consumption by allograft donors may impair osteoinduction and this negative outcome may be worsened by alcohol intake during bone healing. Additionally, PTH has the potential to increase osteoinduction in DBM harvested from both abstinent and alcohol-consuming donors.
FAQ: Alcohol Consumption and Bone Graft Osteoinduction
How does chronic heavy alcohol consumption by bone graft donors affect the ability of demineralized allogenic bone matrix (DBM) to support new bone formation (osteoinduction)?
Chronic heavy alcohol consumption by donor rats significantly impairs the osteoinductive capacity of their DBM. Studies showed that DBM harvested from these donors resulted in lower bone volume formation when implanted into alcohol-naïve recipient rats compared to DBM from control donors. This indicates that alcohol consumption alters the properties of the bone matrix, reducing its ability to stimulate new bone growth.
What are the potential mechanisms by which alcohol consumption impairs the osteoinductive capacity of bone grafts?
The study suggests that one key mechanism involves reduced levels of insulin-like growth factor 1 (IGF-1) within the bone matrix of alcohol-consuming donors. IGF-1 is an important osteoinductive factor, and its decreased concentration in the graft material likely contributes to the impaired bone formation observed in recipients. Alcohol may reduce the deposition of skeletal growth factors into the bone matrix during its formation.
Does alcohol consumption by the recipient of a bone graft further worsen the negative effects of alcohol consumption by the donor?
Yes, the negative impact on bone formation is exacerbated when the recipient also consumes alcohol. When DBM from alcohol-consuming donors was implanted into alcohol-consuming recipients, the resulting bone volume was lower compared to situations where either the donor or the recipient (but not both) had consumed alcohol. This suggests that alcohol intake during the bone healing process further suppresses osteoinduction and graft incorporation.
Can intermittent parathyroid hormone (PTH) treatment counteract the negative effects of alcohol consumption on bone graft incorporation?
The study found that intermittent PTH treatment in recipient rats showed promise in increasing bone volume in critical size defects treated with DBM, regardless of whether the DBM was harvested from control or alcohol-consuming donors. This suggests that PTH has the potential to enhance osteoinduction and bone healing even when the graft material is derived from individuals with a history of heavy alcohol use.
Why is osteoinduction important in the context of bone fractures and bone grafts?
Osteoinduction is a critical process in bone repair as it initiates osteogenesis (new bone formation) at the site of injury. Bone grafts, particularly allografts like DBM, promote osteoinduction by releasing biologically active growth factors present in the graft matrix. This stimulation of new bone formation is essential for the successful healing of complex fractures, critical size defects, and the integration of the bone graft with the host tissue.
How does this research relate to the higher rates of delayed or non-union fractures observed in chronic heavy alcohol consumers?
The findings suggest that the impaired osteoinductive capacity of bone matrix due to chronic alcohol consumption could be a contributing factor to the higher rates of delayed or non-union fractures seen in alcohol abusers. If the bone matrix is less effective at stimulating new bone formation, the natural healing process following a fracture may be compromised.
What are the limitations of this study, and what future research directions are suggested?
Limitations include the focus on chronic heavy alcohol consumption in rats, which may not fully reflect the spectrum of alcohol use in humans, and the fact that the critical size defect study was only performed in male rats. Future research should investigate the influence of other lifestyle factors (e.g., smoking, physical activity) on osteoinduction, explore the potential impact of sex hormones on the skeletal response to DBM during fracture healing, and further elucidate the specific mechanisms beyond IGF-1 that mediate alcohol's effects on bone matrix.
Beyond fracture healing, what implications might the findings have for bone remodeling in individuals with a history of heavy alcohol consumption?
The study suggests that prior heavy alcohol consumption might negatively impact the balance of bone remodeling even after drinking cessation. If alcohol consumption reduces the concentration of critical skeletal coupling factors in the bone matrix, it could hinder the restoration of bone loss that occurred during periods of alcohol abuse, as these factors released during bone resorption are crucial for stimulating subsequent bone formation.