Throughout the day, many people may not think about their bone health and its role in supporting our overall functioning, protecting our organs and helping us move. But for many people living with systemic mastocytosis (SM), this is not an option. Approximately 30 to 50% of SM patients experience abnormal bone density, which could potentially lead to an increased risk of fractures and significantly impact their ability to move without aches and pains.1-3
Our goal to help patients move beyond symptom management and towards disease modification is grounded in targeting the mast cell, a master regulator of the immune system which we believe can crack the code for treating allergic and inflammatory diseases like SM. As we continue investing in mast cell research, the often debilitating nature of SM and its invisible burden – such as the prevalence of abnormal bone density – are becoming increasingly clear.
The connection between mast cells and bone health
Mast cells are essential immune cells that protect the body from disease and infection.4 However, for people living with SM, abnormal mast cells proliferate or activate uncontrollably across organ systems, including in bone marrow, which can lead to a range of symptoms.5 As the presence of abnormal mast cells in bone marrow is almost always involved in SM, a bone marrow biopsy is one way to establish an accurate diagnosis. After a confirmed diagnosis, additional tests which may include a bone scan, skeletal survey or bone density (DXA) scan are usually performed to classify the disease subtype.6
With bone marrow abnormalities proven to be a hallmark of SM, we’re inspired to further explore the role of mast cells in driving this disease and the long-term effects on patients’ bone health.
Abnormal bone health across the spectrum of SM
Osteoporosis (severe low bone density) and osteopenia (moderate low bone density), bone pain and possible fractures have long been recognized in people living with SM.6 When abnormal mast cells proliferate uncontrollably in patients with SM, it can accelerate bone issues.7-8
Approximately 25% of patients with indolent systemic mastocytosis (ISM) experience osteoporosis, approximately 30% have osteopenia, and about 30% will develop a fragility fracture (fracture due to low-impact trauma) at some point in their life.2-3 People living with low bone density conditions often experience back pain and a stooped posture due to bones that break easier than expected.9
Patients with advanced SM (AdvSM) can experience low bone density as well, and one of the diagnostic criteria for AdvSM is the presence of lytic bone lesions and fractures due to mast cell-mediated bone destruction.10-11 However, unlike ISM, some patients with AdvSM can also experience abnormally high bone density, a condition known as osteosclerosis.2 This phenomenon occurs due to the high mast cell infiltration in the bone marrow, leading to increased osteoblast activity and bone formation.12 While osteosclerosis is attributed to higher bone density, it does not make the bones immune to breakage and fracture like what’s seen in osteoporosis.2
These findings highlight the frequency in which patients living with SM experience abnormal bone density conditions, an invisible, long-term disease effect that can significantly impact daily functioning.1-3
Our research to raise awareness of bone health in SM
Through our own research, we aim to further validate the impact of SM on bone health and investigate the promise of targeting mast cells to treat allergic and inflammatory diseases such as SM. At the 2025 AAAAI / WAO Joint Congress, we presented data from our PIONEER clinical trial highlighting the baseline prevalence of low bone density in people living with ISM. Out of 251 patients, about 40% had a medical history of low bone density, with 19% having osteopenia and 22% experiencing osteoporosis. Additionally, 12% of all ISM patients in this study had a history of bone fractures.
In an analysis of 15 patients in PIONEER who were treated at a single trial site and underwent DXA scans to measure bone density, 40% had osteopenia and 20% had osteoporosis at baseline.
“These findings confirm that osteoporosis and osteopenia are significant features of this disease. Based on this data, we’re continuing to explore how targeting the underlying driver of SM may benefit patients who experience low bone density.”
—Ben Lampson, Senior Medical Director at Blueprint Medicines
Additionally at the 2024 ASH Annual Meeting, we shared findings showing baseline levels of bone density in patients with AdvSM. Out of 107 AdvSM patients, 56 received DXA scans at baseline; low bone density was observed in 21% of these patients and high bone density was observed in 38%.
Our continued commitment to the SM community
As we acknowledge Rare Disease Day, the burden of SM on people’s daily lives is not lost. We are fiercely committed to ongoing research as we aim to improve outcomes and bring new hope to people like Lois who seek a fuller life with more possibilities:
“Beginning in my mid-twenties, I have had bone pain that is mild to bone-crushing and has sent me to many doctors. One day, with less bone pain, I hope to play the piano every day, finish the music I write, sing when and where I want to, walk on the beach, dance with my husband, go swimming in a pool even if it is chlorinated, lay on a beach to feel the warmth of the sun, go to the theater and concerts, and be at every family function.”
—Lois, living with SM