Rheumatic DiseaseNCT02504879
Natural History, Pathogenesis and Outcome of Melorheostosis A Rare Osteosclerotic Disease
An observational study of Rheumatic Disease, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
Trial summary
Background: The rare disease melorheostosis causes bones to thicken. This may lead to pain, and can affect bones, joints, and muscles. Researchers want to learn more about the disease and how it progresses. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatic Disease
- How many people
- 350 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2015to 1 Jul 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients aged > 18 years with possible melorheostosis. Relatives of patients with melorheostosis may be included for genetic testing only
Who may be able to join
- All eligible patients are invited to participate in this protocol. Patients are adults aged > 18 years with possible melorheostosis (suspected or confirmed). Since both men and women are affected with the disease, both sexes will be studied. All ethnic and racial groups are at risk and will be included.
- Relatives of patients with melorheostosis may be included for genetic testing only.
Who cannot join
- Pregnant or lactating women. A pregnancy test is performed in women of childbearing potential (up to age 55) unless they have a history of hysterectomy or tubal ligation.
- Children (age less than 18 years) are excluded.
- Subjects with severe active infection or other co-morbidities that in the opinion of the investigator would warrant exclusion.
- Subjects unable to provide informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Study of the Natural History, Pathogenesis and Outcome of Melorheostosis - a Rare Osteosclerotic Disease
Background:
- The rare disease melorheostosis causes bones to thicken. This may lead to pain, and can affect bones, joints, and muscles. Researchers want to learn more about the disease and how it progresses.
Read more
Objective:
-To see what happens to people with melorheostosis over time and understand the causes of the disease.
Eligibility:
- People 18 and over with melorheostosis.
- Their unaffected relatives.
Design:
- All participants will have a medical history and physical exam.
- Participants who are relatives will give samples of blood or cheek cells.
- Other participants will be in the study for about 1 week.
- They will have blood and urine collected.
- Strength, walking, and range of motion will be measured.
- Participants may also have
- X-rays and scans.
- A pain and neurological evaluation.
- Their skin evaluated by a dermatologist.
- A small sample of bone taken.
- Nerve conduction studies. Small electrodes with to wires will be put on the skin. A metal probe will give a small electrical shock.
- Electromyography. A thin needle will be placed into the muscles.
- An ultrasound, which uses sound waves to examine the muscles and nerves. An ultrasound probe will be placed over the skin.
- A bone scan. They will get a small amount of radioactive fluid through a needle in an arm vein. This fluid travels to the bones. The bones will be photographed in a machine.
- Bone Densitometry, a low-level x-ray.
- Photographs taken.
- A small circle of skin removed with a surgical instrument.
- Questionnaires about their quality of life.
- Participants will be asked to return about every 2 years. At these visits, participants may have blood and urine tests and x-rays.
Read the detailed description
Melorheostosis is a rare osteosclerotic disease resulting in exuberant excessive bone growth with a characteristic radiographic appearance often described as dripping candle wax. As a result of these bony formations, patients report mild-moderate pain that interferes with their routine activities. It is usually diagnosed on radiographs but bone biopsy may be performed to exclude other osteosclerotic diseases and/or osteosarcoma. Deformities, limb-length discrepancy, muscle atrophy, neurological deficit have been reported as complications. A subset of patients have somatic mutations in MAP2K1.
The cause of this disease is not known in all patients, the natural history poorly described and there is no clearly-defined systemic therapy. We propose a prospective observational study to investigate the natural history and pathogenesis of the disease. Subjects will undergo standardized initial evaluation and medically indicated testing. Skin biopsies may be performed to test for known mutations related to melorheotosis, and if negative affected bone and/or skin may be sent for genetic testing for acquired somatic mutations in genes that control bone homeostasis. Enrolled subjects will be followed every two to three years for assessment of disease progression and receive testing and treatment. The study of this rare bone disease offers the potential to generate new insights, provide answers as well as generate new questions into the biology of the skeletal and mineral metabolism.
- Conditions
- Rheumatic Disease
- Keywords
- Osteosclerosis, Hyperostosis, Natural History
- Medical subject headings
- Rheumatic Diseases, Osteosclerosis, Hyperostosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Melorheostosis patients | Patients aged > 18 years with possible and confirmed melorheostosis. | |
| Relatives of patients with melorheostosis | Relatives of patients with melorheostosis may be included for genetic testing only. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease progression
explore etiology and natural history of melorheostosis. Besides MAP2K1, what other genetic changes play a role in the etiology of melorheostosis. Does the disease progress to involve new bones or extend into soft tissues over time or is it static
Measured: end of the study
Secondary outcomes (2)
Identify medication that affect melorheostosis
What medications are most effective to help with pain management in melorheostosis
Measured: end of the study
Identify biomarkers
Can biomarkers of disease activity be ascertained.
Measured: end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study start16 Aug 2015
- Primary completion1 Jul 2030 (estimated)
- Study completion1 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Rheumatic DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Dale M Kobrin, M.D., Principal investigator, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02504879
- Sponsor's protocol ID
- 150165
- Other IDs
- 15-AR-0165
- Status last verified
- 3 Nov 2026
- First submitted
- 21 Jul 2015
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Protocol is silent about IPD sharing
Publications
Faruqi T, Dhawan N, Bahl J, Gupta V, Vohra S, Tu K, Abdelmagid SM. Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders. Biomed Res Int. 2014;2014:670842. doi: 10.1155/2014/670842. Epub 2014 Oct 22.
PubMed 25530967Ihde LL, Forrester DM, Gottsegen CJ, Masih S, Patel DB, Vachon LA, White EA, Matcuk GR Jr. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics. 2011 Nov-Dec;31(7):1865-82. doi: 10.1148/rg.317115093.
PubMed 22084176Jain VK, Arya RK, Bharadwaj M, Kumar S. Melorheostosis: clinicopathological features, diagnosis, and management. Orthopedics. 2009 Jul;32(7):512. doi: 10.3928/01477447-20090527-20.
PubMed 19634844Farrell K, Comis LE, Casimir MM, Hodsdon B, Jimenez-Silva R, Dunigan T, Bhattacharyya T, Jha S. Occupational engagement, fatigue, and upper and lower extremity abilities in persons with melorheostosis. PM R. 2023 May;15(5):587-595. doi: 10.1002/pmrj.12817. Epub 2022 May 30.
PubMed 35403375Jha S, Fratzl-Zelman N, Roschger P, Papadakis GZ, Cowen EW, Kang H, Lehky TJ, Alter K, Deng Z, Ivovic A, Flynn L, Reynolds JC, Dasgupta A, Miettinen M, Lange E, Katz J, Klaushofer K, Marini JC, Siegel RM, Bhattacharyya T. Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations. J Bone Miner Res. 2019 Jan;34(1):145-156. doi: 10.1002/jbmr.3577. Epub 2018 Sep 14.
PubMed 30138550
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Natural History, Pathogenesis and Outcome of Melorheostosis - a Rare Osteosclerotic Disease
- ClinicalTrials.gov ID
- NCT02504879
- Acronym / sponsor ID
- 150165
- Conditions
- Rheumatic Disease
- Keywords
- Osteosclerosis, Hyperostosis, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)US National Institutes of Health
- Study start
- 16 Aug 2015 (actual)
- Primary completion
- 1 Jul 2030 (estimated)
- Study completion
- 1 Jul 2030 (estimated)
- First posted
- 22 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- The rare disease melorheostosis causes bones to thicken. This may lead to pain, and can affect bones, joints, and muscles. Researchers want to learn more about the disease and how it progresses.
Objective:
-To see what happens to people with melorheostosis over time and understand the causes of the disease.
Eligibility:
- People 18 and over with melorheostosis.
- Their unaffected relatives.
Design:
- All participants will have a medical history and physical exam.
- Participants who are relatives will give samples of blood or cheek cells.
- Other participants will be in the study for about 1 week.
- They will have blood and urine collected.
- Strength, walking, and range of motion will be measured.
- Participants may also have
- X-rays and scans.
- A pain and neurological evaluation.
- Their skin evaluated by a dermatologist.
- A small sample of bone taken.
- Nerve conduction studies. Small electrodes with to wires will be put on the skin. A metal probe will give a small electrical shock.
- Electromyography. A thin needle will be placed into the muscles.
- An ultrasound, which uses sound waves to examine the muscles and nerves. An ultrasound probe will be placed over the skin.
- A bone scan. They will get a small amount of radioactive fluid through a needle in an arm vein. This fluid travels to the bones. The bones will be photographed in a machine.
- Bone Densitometry, a low-level x-ray.
- Photographs taken.
- A small circle of skin removed with a surgical instrument.
- Questionnaires about their quality of life.
- Participants will be asked to return about every 2 years. At these visits, participants may have blood and urine tests and x-rays.
Detailed description
Melorheostosis is a rare osteosclerotic disease resulting in exuberant excessive bone growth with a characteristic radiographic appearance often described as dripping candle wax. As a result of these bony formations, patients report mild-moderate pain that interferes with their routine activities. It is usually diagnosed on radiographs but bone biopsy may be performed to exclude other osteosclerotic diseases and/or osteosarcoma. Deformities, limb-length discrepancy, muscle atrophy, neurological deficit have been reported as complications. A subset of patients have somatic mutations in MAP2K1.
The cause of this disease is not known in all patients, the natural history poorly described and there is no clearly-defined systemic therapy. We propose a prospective observational study to investigate the natural history and pathogenesis of the disease. Subjects will undergo standardized initial evaluation and medically indicated testing. Skin biopsies may be performed to test for known mutations related to melorheotosis, and if negative affected bone and/or skin may be sent for genetic testing for acquired somatic mutations in genes that control bone homeostasis. Enrolled subjects will be followed every two to three years for assessment of disease progression and receive testing and treatment. The study of this rare bone disease offers the potential to generate new insights, provide answers as well as generate new questions into the biology of the skeletal and mineral metabolism.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melorheostosis patients | – | –Patients aged > 18 years with possible and confirmed melorheostosis. |
| Relatives of patients with melorheostosis | – | –Relatives of patients with melorheostosis may be included for genetic testing only. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients aged > 18 years with possible melorheostosis. Relatives of patients with melorheostosis may be included for genetic testing only
Key inclusion criteria (2 listed)
- All eligible patients are invited to participate in this protocol. Patients are adults aged > 18 years with possible melorheostosis (suspected or confirmed). Since both men and women are affected with the disease, both sexes will be studied. All ethnic and racial groups are at risk and will be included.
- Relatives of patients with melorheostosis may be included for genetic testing only.
Key exclusion criteria (4 listed)
- Pregnant or lactating women. A pregnancy test is performed in women of childbearing potential (up to age 55) unless they have a history of hysterectomy or tubal ligation.
- Children (age less than 18 years) are excluded.
- Subjects with severe active infection or other co-morbidities that in the opinion of the investigator would warrant exclusion.
- Subjects unable to provide informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Disease progression
Time frame: end of the study
explore etiology and natural history of melorheostosis. Besides MAP2K1, what other genetic changes play a role in the etiology of melorheostosis. Does the disease progress to involve new bones or extend into soft tissues over time or is it static
2 secondary outcomes
Identify medication that affect melorheostosis
Time frame: end of the study
Identify biomarkers
Time frame: end of the study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Background: PubMed 25530967Faruqi T, Dhawan N, Bahl J, Gupta V, Vohra S, Tu K, Abdelmagid SM. Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders. Biomed Res Int. 2014;2014:670842. doi: 10.1155/2014/670842. Epub 2014 Oct 22.
- Background: PubMed 22084176Ihde LL, Forrester DM, Gottsegen CJ, Masih S, Patel DB, Vachon LA, White EA, Matcuk GR Jr. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics. 2011 Nov-Dec;31(7):1865-82. doi: 10.1148/rg.317115093.
- Background: PubMed 19634844Jain VK, Arya RK, Bharadwaj M, Kumar S. Melorheostosis: clinicopathological features, diagnosis, and management. Orthopedics. 2009 Jul;32(7):512. doi: 10.3928/01477447-20090527-20.
- Derived from this study: PubMed 35403375Farrell K, Comis LE, Casimir MM, Hodsdon B, Jimenez-Silva R, Dunigan T, Bhattacharyya T, Jha S. Occupational engagement, fatigue, and upper and lower extremity abilities in persons with melorheostosis. PM R. 2023 May;15(5):587-595. doi: 10.1002/pmrj.12817. Epub 2022 May 30.
- Derived from this study: PubMed 30138550Jha S, Fratzl-Zelman N, Roschger P, Papadakis GZ, Cowen EW, Kang H, Lehky TJ, Alter K, Deng Z, Ivovic A, Flynn L, Reynolds JC, Dasgupta A, Miettinen M, Lange E, Katz J, Klaushofer K, Marini JC, Siegel RM, Bhattacharyya T. Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations. J Bone Miner Res. 2019 Jan;34(1):145-156. doi: 10.1002/jbmr.3577. Epub 2018 Sep 14.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Protocol is silent about IPD sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dale M Kobrin, M.D. principal investigator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatic Disease, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nancy A Spencer ((301) 435-8434, nancy.spencer@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease progression (time frame: end of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02504879, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.