Hypophosphatasia is a rare genetic condition that affects how bones form and stay strong. People with this disease have low levels of an important enzyme called alkaline phosphatase. Surprisingly, some adults with this condition experience sudden hip bone breaks that look similar to fractures seen in people taking certain osteoporosis medications for many years. This review examines why these fractures happen and how they differ from typical weak bone fractures, offering new understanding of how this genetic disease affects bone quality and strength.

The Quick Take

  • What they studied: How a rare genetic disease called hypophosphatasia causes unexpected hip bone fractures in adults, and why these fractures are different from typical weak bone breaks
  • Who participated: This is a review article that examined existing research about adults with hypophosphatasia who have experienced hip fractures. No new patients were studied.
  • Key finding: Adults with moderate hypophosphatasia can develop sudden hip fractures that look like fractures from long-term osteoporosis medication use, even though the underlying bone problems are different from typical weak bones
  • What it means for you: If you or someone you know has hypophosphatasia, understanding this connection may help doctors diagnose and treat hip fractures more effectively. However, this is specialized medical information best discussed with your healthcare provider.

The Research Details

This is a review article, meaning the authors examined and summarized existing scientific research about hypophosphatasia and hip fractures rather than conducting a new study with patients. The researchers looked at the biology, genetics, anatomy, and chemistry of how this rare disease affects bones. They focused on understanding why people with hypophosphatasia get hip fractures that look similar to fractures seen in people taking bisphosphonate medications (common osteoporosis drugs) for many years, even though the underlying bone problems are quite different.

The review examined a puzzling contradiction: while hypophosphatasia can cause soft, poorly mineralized bones (a condition called osteomalacia), the hip fractures that actually occur in adults with this disease don’t show these typical soft bone features. Instead, the bones become overly dense and brittle, similar to what happens in other rare bone diseases. This paradox is the main focus of the review.

Understanding how hypophosphatasia causes hip fractures is important because it’s a rare disease that doctors might not immediately recognize. By examining the bone structure and chemistry in detail, researchers can help doctors identify and treat these fractures more effectively. This knowledge also helps scientists understand how different bone diseases work, which may lead to better treatments.

This is a review article written by experts in bone disease, published in a respected medical journal focused on osteoporosis research. Review articles summarize existing knowledge rather than presenting new experimental data. The strength of this review depends on the quality of the research it examines. Readers should understand that while this provides valuable expert perspective, it doesn’t present new clinical evidence from patient studies.

What the Results Show

The main finding is that adults with moderate hypophosphatasia experience hip fractures that appear similar to atypical femoral fractures (AFFs) seen in people taking bisphosphonate medications long-term. However, the bone problems causing these fractures are fundamentally different. In hypophosphatasia, the bones become excessively dense and brittle due to problems with bone cell function, rather than becoming weak and soft as might be expected from the disease’s effects on bone mineralization.

The review highlights that hypophosphatasia can cause osteomalacia, a condition where bones don’t mineralize properly and become soft. Yet paradoxically, the spontaneous hip fractures that characterize this disease don’t show these typical soft bone features. Instead, the bone becomes overly mineralized and brittle, making it prone to breaking even without significant injury.

The researchers note that the bone abnormalities in hypophosphatasia resemble those seen in osteopetrosis, a different rare disease where bones become excessively dense and hard but also very brittle. This similarity suggests that the problem isn’t simply about bone density, but about the quality and structure of the bone at a microscopic level.

The review identifies several important secondary findings: the severity of hypophosphatasia varies greatly depending on how much alkaline phosphatase enzyme activity remains in the body; the genetic mutations causing the disease correlate with how severe symptoms are; and the fractures in hypophosphatasia involve complex abnormalities in how bone is broken down and rebuilt. The review also notes that the nanoscale crystal structure of bone in hypophosphatasia patients differs from normal bone, which may explain why these bones are brittle despite being dense.

This review builds on previous research showing that hypophosphatasia causes unusual bone problems. It adds new perspective by highlighting the paradox that these patients develop hip fractures resembling those from long-term bisphosphonate use, despite having a completely different underlying disease. The comparison to osteopetrosis is particularly valuable, as it suggests that excessive bone density and brittleness, rather than weakness, may be the primary problem in hypophosphatasia-related fractures.

As a review article, this work summarizes existing research rather than presenting new patient data. The authors note that further research is needed to examine the detailed crystal structure of bone in hypophosphatasia patients and to better understand how fractures heal in these individuals. The review is limited by the relatively small amount of research available on this rare disease. Additionally, because hypophosphatasia is uncommon, large-scale studies are difficult to conduct, which means some conclusions are based on limited patient observations.

The Bottom Line

This review is primarily educational for healthcare providers and researchers rather than providing direct recommendations for patients. However, it suggests that doctors should be aware of hypophosphatasia as a possible cause of unexplained hip fractures, particularly in younger adults. If you have hypophosphatasia or a family history of this condition and experience hip pain or fractures, discuss this research with your doctor to ensure proper diagnosis and treatment. (Confidence level: Moderate - based on expert review of existing research)

This research is most relevant for: people with hypophosphatasia or family members of affected individuals; doctors and specialists who treat bone diseases; and researchers studying rare genetic bone disorders. People taking bisphosphonate medications for osteoporosis should not be concerned about developing hypophosphatasia-like fractures, as this is a separate genetic condition. General readers should understand this is specialized medical information for a rare disease affecting a small population.

This review doesn’t address treatment timelines, as it focuses on understanding how the disease works rather than treating it. If you have hypophosphatasia, the timeline for managing fractures depends on the specific treatment your doctor recommends and your individual healing capacity.

Want to Apply This Research?

  • If you have hypophosphatasia, track any bone pain, fractures, or injuries with dates and severity (1-10 scale). Note activities that trigger pain and any treatments received. This information helps your doctor monitor disease progression.
  • Work with your healthcare provider to develop a safe activity plan that balances exercise (important for bone health) with injury prevention. Document which activities feel safe versus risky, and adjust your routine accordingly.
  • Schedule regular check-ins with your bone specialist to review fracture history, bone density scans, and enzyme levels. Use the app to maintain a timeline of medical visits, test results, and any new symptoms between appointments.

This article reviews scientific research about hypophosphatasia and hip fractures. It is educational information only and should not replace professional medical advice. Hypophosphatasia is a rare genetic condition that requires specialized medical care. If you have symptoms of bone disease, unexplained fractures, or a family history of hypophosphatasia, consult with a qualified healthcare provider or bone specialist for proper diagnosis and treatment. Do not make changes to any current medical treatment based on this information without discussing it with your doctor first.