Broken bones regrow quickly with help of biodegradable implant
Penn State
image:
From left to right, biomedical engineering doctoral student Ethan Gerhard; co-corresponding author and Assistant Research Professor of Biomedical Engineering Su Yan; first author and biomedical engineering doctoral student Hui Xu; and biomedical engineering doctoral student Yuqi Wang pose in the lab. The team worked together to create the bone growth scaffold CitraBoneQMg.
view moreCredit: Caleb Craig/Penn State
UNIVERSITY PARK, Pa. — For most broken bones, bone cells regrow on their own while patients wear a cast or brace to keep the injury steady. But for complex or severe fractures, surgeons may intervene by placing grafts or scaffolds made of biocompatible materials, or by using metal fixation devices to ensure proper bone healing and alignment. Collaborating with orthopedic surgeons, a team led by biomedical engineering researchers at Penn State created CitraBoneQMg, an implantable biodegradable scaffold to support bone regrowth made by combining magnesium and glutamine with citric acid. They published research on their implant, for which they filed a U.S. patent application, in Science Advances.
“By integrating magnesium and glutamine — two small molecules found naturally in the body and in food — with citric acid, we found that the molecules work together to promote bone growth by encouraging increased intracellular energy metabolism,” said first author Hui Xu, a doctoral student in biomedical engineering, who is advised by co-corresponding author Su Yan, assistant research professor of biomedical engineering.
The researchers found that adding magnesium and glutamine to a traditional citric acid-only based implant, which was approved by the U.S. Food and Drug Administration and on the market, increased intracellular energy and helped regulate two energy pathways that are essential for bone growth, AMPK and mTORC1. The pathways act as control systems inside the cell, balancing fuel use so cells have the energy to make new bone.
“The molecules concurrently regulate the two energy pathways, which is different than what normally happens – usually they act as a seesaw, one speeding up while the other slows down,” Xu said. “The scaffold essentially powers up a bone cell: both nutrients act in a synergistic relationship with the citric acid to give stem cells more energy to grow and differentiate to bone cells, leading to better bone regrowth.”
To test CitraBoneQMg, the researchers implanted their experimental scaffold into a cranial defect of the skull of rats and compared its resulting bone growth to rats with a citric acid only-based scaffold implant and one with a traditional bone material implant.
They found that after 12 weeks, CitraBoneQMg had increased the bone growth surrounding the cranial injury by 56% as compared to the animals with the citric acid only-based scaffold and 185% compared to the animals with a traditional bone material implant.
“The three molecules work as a healing recipe for the bone, paving the way for a new way of thinking of bone repair,” Yan said. “Alongside rapid bone growth, we also saw nerve regeneration and antiinflammation properties at the site of the scaffold, two elements that are important to long-term healing of the bone.”
Releasing the molecules directly at the site of the injury via the scaffold helps transport a high concentration of nutrients directly to where they are most needed, the researchers explained, rather than relying on oral ingestion, where only a small percentage reaches the injury site.
Additionally, the researchers discovered that the polymer scaffold contains inherent photoluminescent and photoacoustic properties, which allows it to be easily imaged after it is implanted at the injury site.
“With photoacoustic properties, CitraBoneQMg has great potential for in vivo tracking, where it can be detected by ultrasound underneath deep tissue,” Xu said.
In addition to Xu and Yan, the Penn State-affiliated co-authors include Ethan Gerhard, Rohitraj Ray and Yuqi Wang, doctoral students in biomedical engineering; Sri-Rajasekhar Kothapalli, associate professor of biomedical engineering; and April D. Armstrong, the C. McCollister Evarts Professor and chair of the Department of Orthopaedics and Rehabilitation and chief of the Shoulder and Elbow Service, Penn State Health. For a full list of authors and their affiliations, as well as the funding agencies that supported this research, see Science Advances.
A test tube contains the CitraBoneQMg bone implants researchers used in the study.
Credit
Caleb Craig/Penn State
Journal
Science Advances
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Metabotissugenic citrate biomaterials orchestrate bone regeneration via citrate-mediated signaling pathways
New research highlights critical role of
movement in lifelong bone health
Reducing sedentary behaviour and increasing physical activity found to protect against bone loss and fractures across all ages.
A new review by the International Osteoporosis Foundation (IOF) Rehabilitation Working Group underscores the powerful impact of lifestyle behaviours—specifically physical activity and sedentary behaviour —on bone health across the human lifespan.
While exercise has long been recognized for its role in strengthening bones and reducing fracture risk, emerging evidence reveals that prolonged sitting and inactivity can harm skeletal health, even among individuals who engage in regular physical activity.
The study 'The Impact of Sedentary Behavior and Physical Activity on Bone Health: A Narrative Review from the Rehabilitation Working Group of the International Osteoporosis Foundation' synthesizes findings from epidemiological studies, systematic reviews, and meta-analyses, examining how physical activity and sedentary behaviour influence bone mineral density (BMD) and fracture risk in children, adolescents, adults, and older populations.
Key findings include:
- Physical activity – especially weight-bearing and resistance training – improves bone mineral density and helps reduce fracture risk in both younger and older populations.
- Sedentary behaviour – independent of overall activity levels – has harmful effects on bone health, increasing fracture risk, particularly in frail or pre-frail individuals.
- Even light-intensity activity can yield measurable benefits when it replaces sedentary time, especially in older adults and postmenopausal women.
- Early and continuous promotion of physical activity, aligned with World Health Organization (WHO) guidelines, provides an effective strategy for maintaining skeletal health and preventing osteoporotic fractures.
The evidence demonstrates that physical activity and sedentary behaviour are independent, modifiable factors influencing skeletal health. Clinical practice and public health policy should address both — not only encouraging physical activity, but also actively reducing prolonged sedentary time.
Professor Olivier Bruyère, Co-chair of the IOF Rehabilitation Working Group and Lead Author of the publication, stated:
“This review highlights a critical message for populations worldwide: bone health depends not only on engaging in regular physical activity, but also on reducing the hours we spend in sedentary behaviour. In children and adolescents, too much sitting time can undermine bone development, while in adults and older individuals, inactivity accelerates bone loss and fracture risk. Importantly, even light daily activity—such as walking—can provide measurable benefits, particularly for older adults and postmenopausal women.”
IOF President Professor Nicholas Harvey and IOF CSA Chairman Professor Eugene McCloskey jointly underscore the significance of the study’s clinical and policy implications:
“The findings highlight the imperative for early intervention and sustained promotion of physical activity throughout the life course, in alignment with WHO recommendations. We therefore urge governments, healthcare providers, and policymakers to implement comprehensive public health strategies that not only encourage active lifestyles but also systematically reduce sedentary behaviours across all populations and age groups, in order to ensure optimal skeletal health and fracture prevention.”
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Reference: Bruyère, O., Scott, D., Papaioannou, A. et al. The Impact of Sedentary Behavior and Physical Activity on Bone Health: A Narrative Review from the Rehabilitation Working Group of the International Osteoporosis Foundation. Calcif Tissue Int 116, 109 (2025). https://doi.org/10.1007/s00223-025-01421-6
About IOF
The International Osteoporosis Foundation (IOF) is the world’s largest nongovernmental organization dedicated to the prevention, diagnosis, and treatment of osteoporosis and related musculoskeletal diseases. IOF’s membership committees include leading scientific experts, 340 patient organizations and medical societies in more than 150 countries, as well as universities worldwide. The IOF Capture the Fracture® initiative counts over 1,200 Fracture Liaison Services across all regions of the world. Together, this global network works to prioritize bone health and fracture prevention, sharing a vision of a world free from fragility fractures, where healthy mobility is a reality for all. @iofbonehealth
Websites: www.osteoporosis.foundation ; www.capturethefracture.org ; www.worldosteoporosisday.org ; www.buildbetterbones.org ; https://www.iofacademy.org/
Journal
Calcified Tissue International
Method of Research
Literature review
Subject of Research
People
Article Title
The Impact of Sedentary Behavior and Physical Activity on Bone Health: A Narrative Review from the Rehabilitation Working Group of the International Osteoporosis Foundation
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