Researchers studied how ketogenic diets (very low-carb, high-fat eating plans) affect bone health in developing rats, with different results for males and females. Female rats on this diet showed better bone-building cells, while male rats had weaker bone repair abilities. Interestingly, a natural substance called beta-hydroxybutyrate that the body makes during ketogenic diets helped protect bone cells when blood sugar was low. The findings suggest that restrictive diets might affect bone development differently depending on sex, especially during pregnancy and childhood growth.

The Quick Take

  • What they studied: Whether ketogenic diets (eating very few carbohydrates) affect bone-building cells differently in male versus female developing rats, and whether a natural chemical made during ketogenic diets protects these cells.
  • Who participated: Young Wistar rats (a common laboratory rat breed) at 30 days old, studied during pregnancy, nursing, and early development. The study examined bone marrow cells—the tissue inside bones that creates new bone cells.
  • Key finding: Female rats on ketogenic diets showed stronger bone-building activity, but male rats showed weaker bone repair. However, a natural ketone body called beta-hydroxybutyrate protected bone cells from damage when blood sugar was very low.
  • What it means for you: If you’re considering very restrictive diets like ketogenic eating, especially during pregnancy or childhood, talk to your doctor. Boys and girls may respond differently to these diets when it comes to bone health. This research suggests caution with extreme diets for bone-related health goals.

The Research Details

Scientists fed female rats a ketogenic diet (very high fat, moderate protein, very low carbohydrates) before and during pregnancy, then studied the bone marrow cells of their offspring at 30 days old. They compared bone cells from young rats that ate this diet to those that didn’t. They also grew bone marrow cells in laboratory dishes with and without beta-hydroxybutyrate (a chemical the body makes during ketogenic diets) to see how it affected cell behavior.

The researchers measured several things: how well bone cells could build new bone (osteogenic differentiation), how active the cells that break down bone were (osteoclasts), how well cells multiplied, and how healthy the cells stayed under low-sugar conditions. They looked separately at results from male and female rats to see if there were sex differences.

This approach allowed them to study both the long-term effects of ketogenic diets during development and the short-term effects of the ketone body beta-hydroxybutyrate on bone cells in controlled laboratory conditions.

This research matters because ketogenic diets are becoming very popular for weight loss, but we don’t fully understand how they affect bone health—especially in growing children and during pregnancy. By studying bone marrow cells specifically, scientists can understand the basic mechanisms of how these diets work at the cellular level. Testing male and female rats separately is important because hormones and biology differ between sexes, and this could explain why some people respond differently to diets.

This study was published in Scientific Reports, a well-respected scientific journal. The research used controlled laboratory conditions and measured multiple markers of bone health. However, this is animal research using rats, not humans, so results may not directly apply to people. The study examined bone cells in detail but didn’t measure overall bone strength or density in living animals. The sample size of rats wasn’t specified in the abstract, which limits our ability to assess statistical power.

What the Results Show

In female rats that ate ketogenic diets during pregnancy and nursing, their offspring showed bone marrow cells that were better at building new bone and had less activity from cells that break down bone. This suggests female rats’ bones might actually benefit from ketogenic diet exposure during development.

In male rats, the opposite happened: their bone marrow cells showed reduced ability to repair and regenerate bone, even though they also lost body weight like the females. This sex difference was unexpected and suggests that ketogenic diets may affect developing male and female skeletons differently.

When researchers added beta-hydroxybutyrate (the main ketone body produced during ketogenic diets) to bone cells growing in low-sugar conditions, it had protective effects. The cells built more bone matrix (the structure of bone), multiplied better, and stayed healthier. Beta-hydroxybutyrate also reduced inflammation and decreased activity of bone-breaking cells.

Importantly, both male and female rats lost significant body weight on the ketogenic diet, showing the diet was working as intended for weight loss, but the bone cell effects were different between sexes.

The study found that low glucose (blood sugar) alone was harmful to bone cells—it reduced their ability to survive and function. However, when beta-hydroxybutyrate was added to the low-glucose environment, it reversed this damage. This suggests the ketone body itself, not just the low carbohydrate state, provides protection to bone cells. The protective effects of beta-hydroxybutyrate were seen in both young and adult rat bone cells, indicating this benefit might apply across different ages.

Previous research showed that ketogenic diets can reduce bone mass in some people, which is concerning since reduced bone density increases fracture risk. This new study helps explain why: the effects depend on sex and may involve the balance between bone-building and bone-breaking cells. The protective effects of beta-hydroxybutyrate are relatively new findings and suggest that not all effects of ketogenic diets on bone are negative—some components may actually help bone cells survive stress.

This research was conducted in rats, not humans, so we cannot directly apply these findings to people without further study. The study examined bone cells in laboratory dishes and in young developing animals, but didn’t measure actual bone strength or density in living rats over time. The specific ketogenic diet used (low protein version) may not match all ketogenic diets people follow. The study didn’t examine how long these effects last or whether they persist into adulthood. Additionally, the abstract doesn’t specify how many rats were studied, making it difficult to assess whether the findings are statistically reliable.

The Bottom Line

Based on this research (moderate confidence): If you’re considering a ketogenic diet, especially if you’re pregnant, nursing, or have children, discuss bone health with your doctor. Don’t use restrictive diets specifically for bone health without medical guidance. If you do follow a ketogenic diet, ensure adequate protein intake and monitor bone health with your healthcare provider. This research suggests that short-term fasting or extreme carbohydrate restriction may not be ideal for bone development, particularly in males.

This research is most relevant to: pregnant women considering ketogenic diets, parents of growing children, people with diabetes or obesity (who often have bone health concerns), and anyone considering long-term restrictive diets. People with a family history of osteoporosis or bone problems should be especially cautious. This research is less immediately relevant to healthy adults doing short-term ketogenic diets, though the findings suggest caution is warranted.

Bone changes from diet typically develop slowly over weeks to months. If you’re considering dietary changes, give your body at least 3-6 months to adapt, and have bone health checked annually if following restrictive diets long-term. The protective effects of beta-hydroxybutyrate on bone cells appeared relatively quickly in laboratory conditions, but real-world benefits would take longer to manifest.

Want to Apply This Research?

  • If following a ketogenic diet, track weekly body weight, energy levels, and any bone or joint discomfort. Monthly, note any changes in muscle strength or bone pain. This helps identify whether the diet is affecting your bone health.
  • If you choose to follow a ketogenic diet, ensure you’re eating adequate protein (your doctor can recommend the right amount) and include calcium-rich foods. Consider adding a bone health supplement if recommended by your doctor. Track your protein intake daily to ensure you’re not following the ’low protein’ version that showed negative bone effects in this study.
  • Set quarterly reminders to assess bone health markers: ask your doctor about bone density screening if you’re on restrictive diets long-term, track any increases in fractures or bone pain, monitor energy levels and muscle strength monthly, and maintain a food diary to ensure adequate calcium and protein intake.

This research was conducted in laboratory rats and has not been tested in humans. The findings suggest potential concerns about ketogenic diets and bone health, particularly in males and during pregnancy, but more human research is needed before making clinical recommendations. If you are pregnant, nursing, have children, or have existing bone health concerns, consult your healthcare provider before starting a ketogenic diet or any restrictive eating plan. This information is for educational purposes and should not replace professional medical advice. Do not use this research to self-diagnose or self-treat bone conditions.