New Science Reveals How to Build Stronger Bones
For decades, we've accepted bone loss as an inevitable part of aging. Groundbreaking new research is turning this assumption on its head, revealing surprising mechanisms that could keep our skeletons strong throughout life.
Few health concerns are as universally accepted as age-related bone loss. After our mid-20s, we're told, our bones gradually become thinner and more fragile—a seemingly inevitable decline that leads to osteoporosis for millions worldwide. But what if this narrative is incomplete? What if our bodies contain built-in mechanisms for maintaining strong bones throughout life that we're only just beginning to understand?
Recent scientific discoveries have uncovered remarkable new insights into how bones maintain their strength, challenging long-held assumptions about skeletal health. From a newly discovered hormone that builds exceptionally strong bones to specific exercise regimens that can reverse bone loss in postmenopausal women, the science of bone health is undergoing a dramatic transformation. This article explores these groundbreaking developments and what they mean for the future of preventing and treating bone diseases.
Bone is a dynamic living tissue that constantly remodels itself throughout our lives through resorption and formation processes.
Bone is often mistaken for a static, structural material, but in reality, it's a dynamic living tissue that constantly remodels itself throughout our lives. This process involves two key activities: the removal of old bone (resorption) and the formation of new bone (formation). During childhood and adolescence, bone formation outpaces resorption, leading to growth and increased density. By our mid-20s, we reach what is known as peak bone mass—the maximum amount of bone we will ever have 4 7 .
After this peak, the balance between bone formation and resorption begins to shift. In mid-adulthood, the two processes remain relatively balanced, but as we age—particularly for women after menopause—bone resorption can begin to outpace formation, leading to a gradual decline in bone mass 3 4 .
This decline isn't merely a quantitative loss of bone tissue; it also involves structural changes that compromise bone strength. Cortical bone (the dense outer surface) becomes thinner and more porous, while trabecular bone (the spongy interior network of plates and rods) loses connectivity, making it more fragile 3 .
| T-score Range | Category | Fracture Risk |
|---|---|---|
| > -1.0 | Normal Bone Density | Average risk |
| -1.0 to -2.5 | Low Bone Mass (Osteopenia) | Slightly increased risk |
| < -2.5 | Osteoporosis | Significantly increased risk |
Primary hormonal regulator of bone health in women
Why don't breastfeeding women lose bone despite low estrogen?
CCN3 hormone explains the paradox
For decades, estrogen was considered the primary hormonal regulator of bone health in women. The dramatic decline in estrogen during menopause reliably triggers accelerated bone loss, and estrogen therapy can help prevent it 3 . This understanding made a recent observation particularly puzzling to scientists: why don't breastfeeding women experience significant bone loss?
During lactation, calcium is stripped from bones to support milk production, and estrogen levels remain low—conditions that should theoretically lead to rapid bone deterioration. Yet breastfeeding women maintain relatively robust bones. This paradox set researchers on a path to a remarkable discovery 1 .
A research team at UC San Francisco and UC Davis made a breakthrough when studying female mice. They found that blocking a particular estrogen receptor in specific brain neurons led to huge increases in bone mass in female mice 1 5 .
The culprit turned out to be CCN3, a molecule now dubbed the Maternal Brain Hormone (MBH). Crucially, researchers found CCN3 in the same brain region in lactating female mice, explaining how bones remain strong during breastfeeding 1 .
"When we blocked this particular estrogen receptor in female mice, we saw dramatic increases in bone density," said senior author Holly Ingraham, PhD. "One of the remarkable things about these findings is that if we hadn't been studying female mice, which unfortunately is the norm in biomedical research, then we could have completely missed out on this finding" 1 .
The discovery of CCN3's role in bone strength emerged from a sophisticated series of experiments that combined neuroendocrinology, bone biology, and biomedical engineering.
The research began with an observation that female mice with blocked estrogen receptors in hypothalamic neurons developed exceptionally strong bones. The researchers systematically searched for the bone-building factor in these mutant females, eventually pinpointing CCN3 as the responsible hormone 1 .
They confirmed CCN3's role by demonstrating its presence in the same brain region in lactating female mice. When they prevented CCN3 production in lactating mice, the animals rapidly lost bone, and their babies began losing weight 1 .
Researchers tested CCN3's effects across different populations of mice—young, old, male, and female—by increasing circulating CCN3 levels. In all cases, bone mass and strength increased dramatically over weeks 1 .
The team developed a novel delivery system using a hydrogel patch that could be applied directly to fracture sites, releasing CCN3 slowly over two weeks 1 .
They examined the cellular mechanisms by exposing bone stem cells to CCN3 and observing their behavior 1 .
CCN3 dramatically increased bone mass and strength in all types of mice, even doubling bone mass in some female mice that lacked all estrogen or were very old 1 .
The bones formed under CCN3 influence weren't just larger; they were structurally stronger. "When we tested these bones, they turned out to be much stronger than usual," reported Thomas Ambrosi, PhD 1 .
The hydrogel patch with CCN3 spurred youthful healing of fractures in elderly mice, whose fractures normally heal poorly 1 .
At the cellular level, stem cells responsible for generating new bone were much more likely to produce new bone cells when exposed to CCN3 1 .
| Research Tool | Function in Research |
|---|---|
| CCN3 (Maternal Brain Hormone) | The newly discovered hormone tested for its bone-building properties |
| Hydrogel Patch | Innovative delivery system that slowly releases CCN3 at fracture sites |
| Progesterone Receptor Knockout Mice | Specialized animal models that helped identify bone-building mechanisms |
| DEXA Scan | Gold standard for measuring bone mineral density and detecting changes |
| Skeletal Stem Cells | Cellular models used to understand mechanisms of bone formation |
While pharmaceutical applications of CCN3 represent the future of bone health, current strategies for maintaining bone strength remain crucial. Among these, specific types of exercise have proven remarkably effective at building and maintaining bone density.
The key lies in understanding the principles of osteogenic loading—the concept that bone adapts to mechanical stress by becoming stronger. Not all exercise equally benefits bones; effective regimens must apply higher strains at rapid frequencies in weight-bearing positions 8 .
Bone adapts to mechanical stress by becoming stronger
A comprehensive 2025 network meta-analysis analyzing 49 studies across 3,360 postmenopausal women revealed which exercise approaches prove most effective for maintaining bone density :
| Exercise Type | Effect on Lumbar Spine BMD | Relative Efficacy |
|---|---|---|
| Aerobic + Resistance Training | Significant improvement | Most effective |
| Aerobic Exercise Alone | Significant improvement | Moderately effective |
| Resistance Training Alone | Significant improvement | Less effective than combined training |
| Whole Body Vibration | Minimal improvement | Limited effect |
The most promising results come from High-intensity Resistance and Impact Training (HiRIT) programs. These supervised programs incorporate exercises like deadlifts, back squats, and overhead presses performed in weight-bearing positions, combined with high-impact jump exercises 8 .
Contrary to traditional concerns about safety, research shows HiRIT is not only effective but safe and well-tolerated in postmenopausal women with osteoporosis or osteopenia when properly supervised 8 .
The benefits extend beyond bone density to include improved balance and reduced fall risk—particularly important since over 90% of hip fractures occur due to falls 8 .
Based on meta-analysis of 49 studies with 3,360 postmenopausal women
The discovery of CCN3's bone-building properties opens exciting new avenues for treating bone-weakening conditions. Researchers are optimistic that this hormone could help diverse populations, including postmenopausal women, breast cancer survivors taking hormone blockers, elite female athletes, and older men 1 .
"There are some situations where highly mineralized bones are not better; they can be weaker and actually break more easily," explained Dr. Thomas Ambrosi. "But when we tested these bones, they turned out to be much stronger than usual" 1 .
Future research will explore CCN3's molecular mechanisms, its levels in breastfeeding women, and its potential for treating various bone conditions. The UC Davis team also wants to investigate whether CCN3 can help regenerate cartilage, potentially offering new treatments for osteoarthritis 5 .
As this research progresses, the message for current bone health remains clear: targeted exercise combined with adequate nutrition provides a powerful strategy for maintaining bone strength at any age. The combination of impact and resistance exercise should be advocated for osteoporosis prevention, while those with established osteoporosis can benefit from tailored exercise programs focused on improving balance, mobility, and posture 9 .
The traditional narrative of inevitable bone decline is being rewritten by science. From the unexpected discovery of a powerful bone-building hormone in lactating mice to the proven effectiveness of high-intensity exercise in postmenopausal women, research continues to reveal our skeleton's remarkable capacity for strength and regeneration throughout life.
While pharmaceutical applications of CCN3 may be years away, current strategies—particularly specific exercise regimens—already offer powerful tools for building and maintaining bone strength. The future of bone health looks increasingly bright, promising approaches that could help millions maintain stronger, more resilient skeletons throughout their lives.
As Dr. Ingraham reflects on her team's discovery: "It would be incredibly exciting if CCN3 could increase bone mass in all these scenarios" 1 .