Diagnosis
Women with osteoporosis face increased Alzheimer’s risk, study suggests
Women with osteoporosis may be more likely to carry a gene linked to Alzheimer’s, according to new research.
Scientists found that APOE4, the most common genetic risk factor for Alzheimer’s, can weaken bone quality in women, even when standard scans appear normal.
The study, carried out by researchers at the Buck Institute for Research on Ageing in California, US, and UC San Francisco, suggests the gene may damage bone at a microscopic level long before any visible signs.
These changes can emerge as early as midlife and remain invisible to routine imaging tests used to assess bone strength.
The findings suggest a link between Alzheimer’s risk and skeletal health and could help pave the way for earlier detection of both conditions.
Professor Birgit Schilling, a senior author of the study, said: “What makes this finding so striking is that bone quality is being compromised at a molecular level that a standard bone scan simply will not catch.
“APOE4 is quietly disrupting the very cells responsible for keeping bone strong – and it is doing this specifically in females, which mirrors what we see with Alzheimer’s disease risk.”
Doctors have long observed that people with Alzheimer’s suffer higher rates of bone fractures, while osteoporosis in women is known to be one of the earliest predictors of the disease.
Now scientists believe they may have uncovered why.
Researchers led by Dr Charles Schurman carried out a detailed analysis of proteins in aged mouse bone and found that tissue was unusually rich in molecules linked to neurological disease, including those associated with Alzheimer’s.
In particular, long-lived bone cells known as osteocytes showed elevated levels of APOE, with levels twice as high in older female mice compared with younger or male animals.
Further experiments using genetically modified mice revealed that APOE4 had a strong and sex-specific impact on both bone and brain tissue.
The disruption at the protein level was even greater in bone than in the brain.
However, the bone structure itself appeared completely normal under scans.
Instead, the gene interfered with a key maintenance process inside bone cells, preventing them from repairing microscopic channels that keep bones strong and resilient.
When this process breaks down, bones become more fragile even if they look healthy on standard imaging.
These results suggest bone cells could potentially act as early biological warning signs of cognitive decline in women carrying APOE4.
Professor Lisa Ellerby, another senior author, said: “We think targeting these cells may open a new front in preserving bone quality in this population.”
Experts say the findings highlight the need to view the body as an interconnected system rather than treating diseases in isolation.
Dementia, of which Alzheimer’s is the most common form, remains one of the UK’s biggest health challenges.
Around 900,000 people are currently living with the condition, a figure expected to rise to 1.6 million by 2040.
It is already the leading cause of death, responsible for more than 74,000 deaths each year.
Type 2 diabetes diagnoses are rising twice as fast in women under 40 as in women over 40, new data shows.
Type 2 diabetes is a serious condition and can lead to complications such as heart attacks and strokes. When it develops in younger people, it can be more aggressive and have more severe and acute effects.
Diagnoses in women under 40 rose by 47 per cent between 2017/18 and 2023/24. By comparison, diagnoses rose by 22 per cent in women aged 40 to 79.
During the same period, type 2 diabetes diagnoses in men under 40 increased by 34 per cent.
Diabetes UK said it is concerned about the follow-up care offered to women who have had gestational diabetes, also known as GDM, which increases the risk of developing type 2 diabetes after pregnancy.
Gestational diabetes is high blood sugar that develops during pregnancy and usually goes away after birth, but it raises the risk of type 2 diabetes later.
Colette Marshall, chief executive at Diabetes UK, said: “These figures should be a wake-up call. Type 2 diabetes is rising twice as fast in younger women compared to older women, and a crucial opportunity for prevention is being missed. Every diagnosis is life-changing, but when it develops in younger people, type 2 diabetes is even more aggressive.
“Pregnancy shouldn’t be a pathway to ill health. Yet despite facing a much higher risk of type 2 diabetes, too many women with GDM receive little or no follow-up care after pregnancy.
“As the Government turns its Strategy into action, support for women who have had gestational diabetes must not be overlooked.”
Last year, the NHS published the first national GDM audit for England in 2024/25, which revealed inconsistencies in follow-up care.
Only 57 per cent of women with GDM received an annual HbA1c test, which should be offered to every woman with GDM.
An HbA1c test measures average blood sugar levels over the previous two to three months.
Only 4.5 per cent of women had received support through the NHS Diabetes Prevention Programme.
The report also found that 11 per cent of women developed prediabetes within five years of having GDM, while 15 per cent developed type 2 diabetes within 10 years.
Prediabetes means blood sugar levels are higher than normal and a person has a higher risk of developing type 2 diabetes.
A recent survey funded by Diabetes UK also found that more than a third of women with GDM felt abandoned by healthcare services after giving birth.
If you live in England and have had gestational diabetes, you can self-refer to the NHS Diabetes Prevention Programme, which supports people at risk of developing type 2 diabetes. If you live in Northern Ireland, Scotland or Wales, you can speak to your GP about support.
Diabetes UK has written to women’s health minister Baroness Merron calling for urgent improvements to postnatal support for those diagnosed with GDM during pregnancy.
GDM affects between 10 and 20 per cent of pregnant women, but Diabetes UK said cases have long been underreported and UK-wide data on the condition has not been readily available.
The charity said poor follow-up care for women who have had GDM may be contributing to rising rates of type 2 diabetes in younger women.
It is calling for consistent postnatal follow-ups for women after GDM, more referrals to the NHS Diabetes Prevention Programme, greater accountability for improvements in postnatal care, and action on inequalities affecting women from deprived and minority ethnic communities.
A genomic test may help some women with breast cancer avoid chemotherapy, with near-identical outcomes in an international trial.
The findings suggest patients with a low test score could be treated with hormone therapy alone without increasing the risk of their cancer returning.
Researchers said the results could support more personalised treatment decisions and spare some women the side-effects of chemotherapy.
Prof Rob Stein, the trial’s chief investigator and a professor of breast oncology at UCL, said: “Optima addresses a longstanding challenge in breast cancer care: identifying who truly benefits from chemotherapy and who does not.
“Our findings show that many patients can safely avoid chemotherapy without compromising their outcomes.
“These results mark an important and significant step toward more personalised treatment.
“The trial has successfully used tumour biology to guide decisions rather than relying solely on traditional clinical features.”
Breast cancer treatment usually involves surgery to remove tumours. Chemotherapy is then often recommended if doctors believe there is a risk the disease will return.
Chemotherapy can cause side-effects including hair loss, rashes, nausea, insomnia and fatigue. Some women may also face longer-term consequences such as infertility, cognitive impairment or early menopause.
The Optima trial followed more than 4,000 patients with newly diagnosed breast cancer in the UK, Norway, Sweden, Australia, New Zealand and Thailand.
The trial was led by University College London.
One woman who took part in the trial told the Guardian that being able to skip chemotherapy felt “like Christmas”. Nine years after being diagnosed, taking the test and skipping chemotherapy, she is healthy and enjoying a full and active life.
The trial tested whether a genomic test could identify which patients need chemotherapy and which could safely avoid it.
The Prosigna test, made by diagnostics company Veracyte, analyses the activity of 50 genes in tumour tissue. It identifies the molecular subtype of the cancer and gives a score estimating the risk of breast cancer returning in the next 10 years.
The randomised trial involved 4,429 patients aged 40 or over with hormone-positive breast cancer. Hormone-positive breast cancer grows in response to hormones such as oestrogen or progesterone. It is the most common form of breast cancer, accounting for up to 80 per cent of cases globally.
Participants were assigned to one of two groups. In the standard treatment group, patients received chemotherapy followed by hormone therapy.
In the second group, patients had their tumours analysed using the genomic test. Those with a high score received chemotherapy and hormone therapy. Those with a low score received hormone therapy alone.
Radiotherapy and other treatments were given as usual in both groups.
In the second group, outcomes were very similar whether chemotherapy was given or not. Five years after treatment, 95 per cent of patients who had chemotherapy and hormone therapy were alive and free from breast cancer recurrence, while 94 per cent of those who skipped chemotherapy were also alive and recurrence-free.
The findings suggest chemotherapy offered little or no additional benefit for patients with low test scores.
Some men also took part in the study, but researchers said there were too few to draw firm conclusions for this group.
The trial received funding from the National Institute for Health and Care Research, Veracyte and cancer charities.
Prof Iain MacPherson, a co-chief investigator and professor of breast oncology at the University of Glasgow, said: “Optima provides robust, practice-changing evidence that we can safely reduce the use of chemotherapy for many patients with hormone-sensitive breast cancer.
“These findings represent a major step forward in delivering more personalised, precise care, ensuring that treatment decisions are driven by what will genuinely improve outcomes for patients, while avoiding unnecessary toxicity.
“The potential impact for both patients and health services is substantial.”
The FDA has delayed approval of camizestrant while it reviews new analyses submitted by AstraZeneca after advisers voted against the breast cancer drug.
The US regulator had been considering whether to approve the oral treatment after a phase 3 switching study in a specific group of breast cancer patients.
Camizestrant is an oral SERD, or selective oestrogen receptor degrader. These drugs are designed to block and break down oestrogen receptors that can help some breast cancers grow.
AstraZeneca filed for approval based on the phase 3 Serena-6 trial, which tested a treatment-switching approach.
Patients in the study received an aromatase inhibitor and a CDK4/6 inhibitor. Aromatase inhibitors lower oestrogen levels, while CDK4/6 inhibitors are targeted cancer drugs that help slow cancer cell growth.
After detecting an ESR1 mutation, investigators switched the aromatase inhibitor to camizestrant.
An ESR1 mutation is a change in a gene linked to the oestrogen receptor. It can make some breast cancers less responsive to standard hormone treatments.
AstraZeneca said switching to camizestrant was linked to a 56 per cent increase in progression-free survival.
Progression-free survival measures how long a patient lives without their disease getting worse.
However, the FDA raised questions about the study design.
An FDA advisory committee later voted six to three that AstraZeneca had failed to show camizestrant provides a clinically meaningful benefit.
The vote was a setback for the company’s hopes of approval, although the FDA can go against advisory committee recommendations.
After the setback, AstraZeneca submitted additional analyses requested by the FDA.
The company said the analyses include data on circulating tumour DNA clearance linked to longer-term efficacy outcomes.
Circulating tumour DNA refers to fragments of genetic material from cancer cells that can be found in the blood.
AstraZeneca is expected to share the data next week at the American Society of Clinical Oncology annual meeting.
The FDA has now delayed its ruling while it reviews the additional information. AstraZeneca did not provide a new decision date.
Three-month delays are typical and, during the second Trump administration, have been common.
After budget cuts reduced its workforce, the FDA delayed rulings on assets including Bayer’s Lynkuet, Biohaven’s troriluzole and Sanofi’s tolebrutinib. The FDA reportedly blamed a “heavy workload and limited resources” for one delay.
The agency has continued to delay rulings this year, with Biogen, Savara and Travere Therapeutics among the companies to say the FDA has extended reviews of their drugs.
Like AstraZeneca, those three companies faced delays after submitting additional information that the agency needed time to review.
If the additional analyses address the regulator’s concerns, AstraZeneca could still secure approval for a drug it has estimated could generate peak sales of more than US$5bn.
Guggenheim Securities analysts recently described the Serena-6 study as “a limited commercial opportunity in our and [AstraZeneca’s] view”.
AstraZeneca is also running two adjuvant studies and a trial in a first-line setting as it seeks to position camizestrant across different stages of breast cancer care.
Adjuvant treatment is given after primary treatment, such as surgery, to reduce the risk of cancer returning. First-line treatment is the first therapy given for a disease.
Roche reported the failure of its rival oral SERD in first-line breast cancer in March, but AstraZeneca executives have argued that their trial designs and drug candidate are different.
Last week, Europe’s Committee for Medicinal Products for Human Use issued a positive opinion on camizestrant.
The drug is expected to be marketed as Etcamah in Europe.
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