Mitochondrial DiseasesNCT05483738
The Impact of Mitochondrial Dysfunction on Human Bone Cell Metabolism and Remodelling
A study testing Clinical assessment, blood samples, bone marrow and bone biopsy in people with Mitochondrial Diseases and Bone Remodeling Disorder, run by Aalborg University Hospital at 1 site in Denmark.
Trial summary
Cell and mice studies suggest mitochondrial dysfunction may cause altered bone structure. Hypothesis: Decreased mitochondrial energy production affects bone cell development and activity negatively. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Diseases, Bone Remodeling Disorder
- What is being tested?
- Clinical assessment, blood samples, bone marrow and bone biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2020to 1 Dec 2026
- Phase
- Interventional
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Genetic diagnosis with: MT-TL1 m.3243A>G, or POLG variant, het or TWNK variant, het, > 18 years
- Signed informed consent
- Healthy subjects matched on age and gender > 18 years
- Signed informed consent
Who cannot join
- Renal (creatinine > 90 µmol/l)
- Liver dysfunction (AST > 3 times the upper limit)
- Medical treatment influencing bone metabolism (oral corticosteroid <12 weeks, anti-osteoporosis treatment, sex steroids, anti-convulsants)
- Pregnancy
- Excessive consumption of alcohol
- Treatment with anticoagulants
- Pre-existing coagulopathy
- Allergy to lidocaine, morphine or diazepam.
Trial locations and contacts
1 site in 1 country.
About this study
Cell and mice studies suggest mitochondrial dysfunction may cause altered bone structure.
Hypothesis: Decreased mitochondrial energy production affects bone cell development and activity negatively.
Comparing humans with the mitochondrial DNA variant, m.3243A>G, pathogenic variants in POLG or TWNK genes to healthy controls, the aim is to evaluate the effect of mitochondrial dysfunction on: 1: bone-cell development and -activity in bone marrow stem cells and blood.
2: bone cell metabolism including glucose consumption. 3: bone structure assessed by electron microscopy and μCT scans of bone biopsies.
Read the detailed description
Intact mitochondrial activity including adequate energy supplies is vital for metabolic active tissues i.e. skeletal muscle, heart and brain. The human skeleton represent an additional highly metabolically active tissue; nevertheless the significance of the mitochondrial role in human skeletal bone health may be further investigated.
Bone remodelling constitutes the coupled and continuous regenerative process of bone degradation by bone resorbing cells osteoclasts (OC) followed by formation of bone matrix by bone forming osteoblasts (OB). Quantitative imbalance between resorption and formation results in skeletal disorders with low bone mass including osteoporosis, and its increased risk of fragility fractures.
Mitochondria generate cellular energy adenosine triphosphate (ATP) through oxidative phosphorylation process (OXPHOS) in the respiratory chain (RC) with a secondary production of the deleterious by-products free radicals i.e. reactive oxygen species (ROS). Notably, mitochondria hold their own DNA (m.DNA), and RC subunits are encoded by m.DNA and nuclear DNA (n.DNA) genes, respectively. With ageing, deleterious somatic m.DNA mutations accumulate in skeletal muscle and heart, and somatic m.DNA mutations as well as inherited m.DNA or n.DNA mutations may result in mitochondrial dysfunction with impaired ATP production and accumulation of ROS. m.DNA mutations may impair brain, skeletal-, and cardiac muscle function, but the effects on human bone cell metabolism and remodelling are unknown. A recent study of a cohort of young individuals indicates that mitochondrial diseases pose a risk for bone fragility fractures.
Preclinical studies suggest that ATP and ROS regulate bone metabolism. The m.DNA number and mitochondrial activity increase to support differentiation from human skeletal (mesenchymal) stem cells (hMSC) to mature bone forming OBs. Inhibition of mitochondrial activity or increase in ROS levels suppress OB differentiation. Similarly, OCs are rich in mitochondria. Human OC cultures demonstrate that energy supplies for OC differentiation from their progenitors is based on OXPHOS while OC resorption activity relies on glycolysis.
In addition, emerging evidence suggest that metabolic plasticity i.e. regulation of glycolysis, OXPHOS, and pyruvate levels, contribute to regulation of OB and OC differentiation.
Receptor activator of nuclear factor kappa-Beta ligand (RANKL) secreted by OBs activates OC resorption. In mice, RANKL stimulation of bone marrow OC progenitors increases intracellular levels of ROS, which stimulates OC differentiation and bone resorption in-vitro. Further, ROS inhibits the wingless-type (Wnt) signalling pathway with attenuation of osteoblastogenesis and decreased bone formation.
Furthermore, mice with mutations in the n.DNA encoded proof reading domain of m.DNA polymerase POLG (PolgA-/-) accumulate m.DNA mutations, and present with premature ageing phenotype including low bone mass. In addition, deficiency of the n.DNA encoded mitochondrial transcription factor (TFAM) causes ATP depletion, and mice with TFAM deficient OCs have increased OC activity and augmented bone resorption. Opposite, global loss of NADH (nicotinamide-adenine dinucleotide) ubiquinone oxidoreductase Fe-S protein 4 (NDUFS4) a subunit in RC complex 1 impairs bone resorption, and (ndufs4-/-) mice present with increased bone mineral density (BMD) and an apparent osteopetrosis bone phenotype.
The aim is to study bone cell phenotype in patients with rare mitochondrial disease Carriers of MT-TL1 m.3243A>G (MIM: 590050).The gene encodes the transcription factor tRNALeu(UUA/UUG) and m.3243A>G weakens the assembly of RC complex with a secondary impaired ATP production. The phenotype is, in part associated with the m.3243A>G mutation burden i.e. level of heteroplasmy (percentage of m.3243A>G/wildtype m.DNA). The study group also includes carriers of mutations in the nuclear encoded POLG (MIM: 174763) and TWNK (MIM: 606075).
Hypothesis: Impaired mitochondrial function affects human bone cell -differentiation, -metabolism, and -activity leading to impaired bone formation and bone fragility.
Aim: To determine if carriers of inherited mitochondrial mutations i.e. mitochondrial dysfunction, ATP depletion and secondary increase in ROS lead to change in:
- In-vitro OB differentiation-rate, OB activity and bone formation.
- In-vitro OC differentiation-, OC activity and higher overall bone resorption.
- In-vivo changes in tissues level dynamics of bone formation and - resorption as examined in iliac crest bone biopsies.
Design, Participants and Methods: Cross-sectional case-control study including subjects (>18 years) carrying one of the following mutations:
- MT-TL1 m.3243A>G
- POLG mutation
- TWNK
N=10 cases with each pathogenic genetic variant and equal number of controls (n=30) matched on sex, age and BMI.
- Conditions
- Mitochondrial Diseases, Bone Remodeling Disorder
- Being tested
- Clinical assessment, blood samples, bone marrow and bone biopsy
- Keywords
- m3243A>G, POLG, TWNK, Mitochondria
- Medical subject headings
- Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical assessment, blood samples, bone marrow and bone biopsyDiagnostic test
Assessment of blood samples, bone marrow and bone biopsy
| Study group | Role | What they receive |
|---|---|---|
| Cases and controls | Other | Clinical assessment, blood samples, dual energy x-ray absorptiometry (DXA) scan, and assessment of bone marrow, and tetracycline labelled bone biopsy Receives: Diagnostic Test: Clinical assessment, blood samples, bone marrow and bone biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extracellular acidification rate (ECAR) (mpH/min)
Measurement of ECAR in human bone marrow skeletal (mesenchymal) stem cells (hBM-MSCs), osteoblasts (OB) and osteoclasts (OC)
Measured: Up to 12 weeks
Oxygen consumption rate (OCR) (mpMol/min)
Measurement of OCR in hBM-MSCs, OBs and OCs
Measured: Up to 12 weeks
Growth rate (number of cells)
Growth rate of of OBs and OCs
Measured: Up to 12 weeks
Secondary outcomes (2)
Bone growth rate (µm/day)
Histomophometric measurements of bone growth in tetracycline labeled bone biopsy
Measured: Up to 4 weeks
Histomorphometric
Histomophometric studies of bone biopsies
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2022
- Study start1 Feb 2020
- Primary completion1 Aug 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- More trials run by Aalborg University HospitalThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Matched case-control study
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital, University of Southern Denmark
- Responsible party
- Principal investigator, Anja Lisbeth Frederiksen, Aalborg University Hospital
- Investigators
- Anja L Frederiksen, MD, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05483738
- Sponsor's protocol ID
- S-20180170
- Status last verified
- Oct 2025
- First submitted
- 22 Jul 2022
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, Suomalainen A, Thorburn DR, Zeviani M, Turnbull DM. Mitochondrial diseases. Nat Rev Dis Primers. 2016 Oct 20;2:16080. doi: 10.1038/nrdp.2016.80.
PubMed 27775730Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006 May 25;354(21):2250-61. doi: 10.1056/NEJMra053077. No abstract available.
PubMed 16723616Bartell SM, Kim HN, Ambrogini E, Han L, Iyer S, Serra Ucer S, Rabinovitch P, Jilka RL, Weinstein RS, Zhao H, O'Brien CA, Manolagas SC, Almeida M. FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation. Nat Commun. 2014 Apr 30;5:3773. doi: 10.1038/ncomms4773.
PubMed 24781012Andreasen CM, Ding M, Overgaard S, Bollen P, Andersen TL. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep. Bone. 2015 Jun;75:32-9. doi: 10.1016/j.bone.2015.02.014. Epub 2015 Feb 14.
PubMed 25689083Kim SJ, Mehta HH, Wan J, Kuehnemann C, Chen J, Hu JF, Hoffman AR, Cohen P. Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging (Albany NY). 2018 Jun 10;10(6):1239-1256. doi: 10.18632/aging.101463.
PubMed 29886458Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 2013 Jul;87(7):1157-80. doi: 10.1007/s00204-013-1034-4. Epub 2013 Mar 30.
PubMed 23543009Meissner C, Bruse P, Mohamed SA, Schulz A, Warnk H, Storm T, Oehmichen M. The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more? Exp Gerontol. 2008 Jul;43(7):645-652. doi: 10.1016/j.exger.2008.03.004. Epub 2008 Mar 20.
PubMed 18439778Lee HC, Wei YH. Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging. Exp Biol Med (Maywood). 2007 May;232(5):592-606.
PubMed 17463155Hayashi G, Cortopassi G. Oxidative stress in inherited mitochondrial diseases. Free Radic Biol Med. 2015 Nov;88(Pt A):10-7. doi: 10.1016/j.freeradbiomed.2015.05.039. Epub 2015 Jun 12.
PubMed 26073122Gandhi SS, Muraresku C, McCormick EM, Falk MJ, McCormack SE. Risk factors for poor bone health in primary mitochondrial disease. J Inherit Metab Dis. 2017 Sep;40(5):673-683. doi: 10.1007/s10545-017-0046-2. Epub 2017 Apr 27.
PubMed 28451918Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH. Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells. 2008 Apr;26(4):960-8. doi: 10.1634/stemcells.2007-0509. Epub 2008 Jan 24.
PubMed 18218821Gao J, Feng Z, Wang X, Zeng M, Liu J, Han S, Xu J, Chen L, Cao K, Long J, Li Z, Shen W, Liu J. SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress. Cell Death Differ. 2018 Feb;25(2):229-240. doi: 10.1038/cdd.2017.144. Epub 2017 Sep 15.
PubMed 28914882Brown D, Breton S. Mitochondria-rich, proton-secreting epithelial cells. J Exp Biol. 1996 Nov;199(Pt 11):2345-58. doi: 10.1242/jeb.199.11.2345.
PubMed 9114500Lemma S, Sboarina M, Porporato PE, Zini N, Sonveaux P, Di Pompo G, Baldini N, Avnet S. Energy metabolism in osteoclast formation and activity. Int J Biochem Cell Biol. 2016 Oct;79:168-180. doi: 10.1016/j.biocel.2016.08.034. Epub 2016 Aug 30.
PubMed 27590854Arnett TR, Orriss IR. Metabolic properties of the osteoclast. Bone. 2018 Oct;115:25-30. doi: 10.1016/j.bone.2017.12.021. Epub 2017 Dec 21.
PubMed 29274806
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Mitochondrial Dysfunction on Human Bone Cell Metabolism and Remodelling
- ClinicalTrials.gov ID
- NCT05483738
- Acronym / sponsor ID
- S-20180170
- Conditions
- Mitochondrial Diseases, Bone Remodeling Disorder
- Keywords
- m3243A>G, POLG, TWNK, Mitochondria
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Collaborators
- Odense University Hospital, University of Southern Denmark
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 1 Aug 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 2 Aug 2022 (actual)
- 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.
Cell and mice studies suggest mitochondrial dysfunction may cause altered bone structure.
Hypothesis: Decreased mitochondrial energy production affects bone cell development and activity negatively.
Comparing humans with the mitochondrial DNA variant, m.3243A>G, pathogenic variants in POLG or TWNK genes to healthy controls, the aim is to evaluate the effect of mitochondrial dysfunction on: 1: bone-cell development and -activity in bone marrow stem cells and blood.
2: bone cell metabolism including glucose consumption. 3: bone structure assessed by electron microscopy and μCT scans of bone biopsies.
Detailed description
Intact mitochondrial activity including adequate energy supplies is vital for metabolic active tissues i.e. skeletal muscle, heart and brain. The human skeleton represent an additional highly metabolically active tissue; nevertheless the significance of the mitochondrial role in human skeletal bone health may be further investigated.
Bone remodelling constitutes the coupled and continuous regenerative process of bone degradation by bone resorbing cells osteoclasts (OC) followed by formation of bone matrix by bone forming osteoblasts (OB). Quantitative imbalance between resorption and formation results in skeletal disorders with low bone mass including osteoporosis, and its increased risk of fragility fractures.
Mitochondria generate cellular energy adenosine triphosphate (ATP) through oxidative phosphorylation process (OXPHOS) in the respiratory chain (RC) with a secondary production of the deleterious by-products free radicals i.e. reactive oxygen species (ROS). Notably, mitochondria hold their own DNA (m.DNA), and RC subunits are encoded by m.DNA and nuclear DNA (n.DNA) genes, respectively. With ageing, deleterious somatic m.DNA mutations accumulate in skeletal muscle and heart, and somatic m.DNA mutations as well as inherited m.DNA or n.DNA mutations may result in mitochondrial dysfunction with impaired ATP production and accumulation of ROS. m.DNA mutations may impair brain, skeletal-, and cardiac muscle function, but the effects on human bone cell metabolism and remodelling are unknown. A recent study of a cohort of young individuals indicates that mitochondrial diseases pose a risk for bone fragility fractures.
Preclinical studies suggest that ATP and ROS regulate bone metabolism. The m.DNA number and mitochondrial activity increase to support differentiation from human skeletal (mesenchymal) stem cells (hMSC) to mature bone forming OBs. Inhibition of mitochondrial activity or increase in ROS levels suppress OB differentiation. Similarly, OCs are rich in mitochondria. Human OC cultures demonstrate that energy supplies for OC differentiation from their progenitors is based on OXPHOS while OC resorption activity relies on glycolysis.
In addition, emerging evidence suggest that metabolic plasticity i.e. regulation of glycolysis, OXPHOS, and pyruvate levels, contribute to regulation of OB and OC differentiation.
Receptor activator of nuclear factor kappa-Beta ligand (RANKL) secreted by OBs activates OC resorption. In mice, RANKL stimulation of bone marrow OC progenitors increases intracellular levels of ROS, which stimulates OC differentiation and bone resorption in-vitro. Further, ROS inhibits the wingless-type (Wnt) signalling pathway with attenuation of osteoblastogenesis and decreased bone formation.
Furthermore, mice with mutations in the n.DNA encoded proof reading domain of m.DNA polymerase POLG (PolgA-/-) accumulate m.DNA mutations, and present with premature ageing phenotype including low bone mass. In addition, deficiency of the n.DNA encoded mitochondrial transcription factor (TFAM) causes ATP depletion, and mice with TFAM deficient OCs have increased OC activity and augmented bone resorption. Opposite, global loss of NADH (nicotinamide-adenine dinucleotide) ubiquinone oxidoreductase Fe-S protein 4 (NDUFS4) a subunit in RC complex 1 impairs bone resorption, and (ndufs4-/-) mice present with increased bone mineral density (BMD) and an apparent osteopetrosis bone phenotype.
The aim is to study bone cell phenotype in patients with rare mitochondrial disease Carriers of MT-TL1 m.3243A>G (MIM: 590050).The gene encodes the transcription factor tRNALeu(UUA/UUG) and m.3243A>G weakens the assembly of RC complex with a secondary impaired ATP production. The phenotype is, in part associated with the m.3243A>G mutation burden i.e. level of heteroplasmy (percentage of m.3243A>G/wildtype m.DNA). The study group also includes carriers of mutations in the nuclear encoded POLG (MIM: 174763) and TWNK (MIM: 606075).
Hypothesis: Impaired mitochondrial function affects human bone cell -differentiation, -metabolism, and -activity leading to impaired bone formation and bone fragility.
Aim: To determine if carriers of inherited mitochondrial mutations i.e. mitochondrial dysfunction, ATP depletion and secondary increase in ROS lead to change in:
- In-vitro OB differentiation-rate, OB activity and bone formation.
- In-vitro OC differentiation-, OC activity and higher overall bone resorption.
- In-vivo changes in tissues level dynamics of bone formation and - resorption as examined in iliac crest bone biopsies.
Design, Participants and Methods: Cross-sectional case-control study including subjects (>18 years) carrying one of the following mutations:
- MT-TL1 m.3243A>G
- POLG mutation
- TWNK
N=10 cases with each pathogenic genetic variant and equal number of controls (n=30) matched on sex, age and BMI.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Matched case-control study
| Arm | Type | Receives |
|---|---|---|
| Cases and controls | Other | Diagnostic Test: Clinical assessment, blood samples, bone marrow and bone biopsyClinical assessment, blood samples, dual energy x-ray absorptiometry (DXA) scan, and assessment of bone marrow, and tetracycline labelled bone biopsy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Genetic diagnosis with: MT-TL1 m.3243A>G, or POLG variant, het or TWNK variant, het, > 18 years
- Signed informed consent
- Healthy subjects matched on age and gender > 18 years
- Signed informed consent
Key exclusion criteria (8 listed)
- Renal (creatinine > 90 µmol/l)
- Liver dysfunction (AST > 3 times the upper limit)
- Medical treatment influencing bone metabolism (oral corticosteroid <12 weeks, anti-osteoporosis treatment, sex steroids, anti-convulsants)
- Pregnancy
- Excessive consumption of alcohol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical assessment, blood samples, bone marrow and bone biopsyAssessment of blood samples, bone marrow and bone biopsy | Diagnostic test | Cases and controls |
Primary outcome
Extracellular acidification rate (ECAR) (mpH/min)
Time frame: Up to 12 weeks
Measurement of ECAR in human bone marrow skeletal (mesenchymal) stem cells (hBM-MSCs), osteoblasts (OB) and osteoclasts (OC)
Oxygen consumption rate (OCR) (mpMol/min)
Time frame: Up to 12 weeks
Measurement of OCR in hBM-MSCs, OBs and OCs
Growth rate (number of cells)
Time frame: Up to 12 weeks
Growth rate of of OBs and OCs
2 secondary outcomes
Bone growth rate (µm/day)
Time frame: Up to 4 weeks
Histomorphometric
Time frame: Up to 4 weeks
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 2 Oct 2025.
- Background: PubMed 27775730Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, Suomalainen A, Thorburn DR, Zeviani M, Turnbull DM. Mitochondrial diseases. Nat Rev Dis Primers. 2016 Oct 20;2:16080. doi: 10.1038/nrdp.2016.80.
- Background: PubMed 16723616Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006 May 25;354(21):2250-61. doi: 10.1056/NEJMra053077. No abstract available.
- Background: PubMed 24781012Bartell SM, Kim HN, Ambrogini E, Han L, Iyer S, Serra Ucer S, Rabinovitch P, Jilka RL, Weinstein RS, Zhao H, O'Brien CA, Manolagas SC, Almeida M. FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation. Nat Commun. 2014 Apr 30;5:3773. doi: 10.1038/ncomms4773.
- Background: PubMed 25689083Andreasen CM, Ding M, Overgaard S, Bollen P, Andersen TL. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep. Bone. 2015 Jun;75:32-9. doi: 10.1016/j.bone.2015.02.014. Epub 2015 Feb 14.
- Background: PubMed 29886458Kim SJ, Mehta HH, Wan J, Kuehnemann C, Chen J, Hu JF, Hoffman AR, Cohen P. Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging (Albany NY). 2018 Jun 10;10(6):1239-1256. doi: 10.18632/aging.101463.
- Background: PubMed 23543009Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 2013 Jul;87(7):1157-80. doi: 10.1007/s00204-013-1034-4. Epub 2013 Mar 30.
- Background: PubMed 18439778Meissner C, Bruse P, Mohamed SA, Schulz A, Warnk H, Storm T, Oehmichen M. The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more? Exp Gerontol. 2008 Jul;43(7):645-652. doi: 10.1016/j.exger.2008.03.004. Epub 2008 Mar 20.
- Background: PubMed 17463155Lee HC, Wei YH. Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging. Exp Biol Med (Maywood). 2007 May;232(5):592-606.
- Background: PubMed 26073122Hayashi G, Cortopassi G. Oxidative stress in inherited mitochondrial diseases. Free Radic Biol Med. 2015 Nov;88(Pt A):10-7. doi: 10.1016/j.freeradbiomed.2015.05.039. Epub 2015 Jun 12.
- Background: PubMed 28451918Gandhi SS, Muraresku C, McCormick EM, Falk MJ, McCormack SE. Risk factors for poor bone health in primary mitochondrial disease. J Inherit Metab Dis. 2017 Sep;40(5):673-683. doi: 10.1007/s10545-017-0046-2. Epub 2017 Apr 27.
- Background: PubMed 18218821Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH. Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells. 2008 Apr;26(4):960-8. doi: 10.1634/stemcells.2007-0509. Epub 2008 Jan 24.
- Background: PubMed 28914882Gao J, Feng Z, Wang X, Zeng M, Liu J, Han S, Xu J, Chen L, Cao K, Long J, Li Z, Shen W, Liu J. SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress. Cell Death Differ. 2018 Feb;25(2):229-240. doi: 10.1038/cdd.2017.144. Epub 2017 Sep 15.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Anja L Frederiksen, MD principal investigator
Aalborg University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clinical assessment, blood samples, bone marrow and bone biopsy in people with Mitochondrial Diseases and Bone Remodeling Disorder, run by Aalborg University Hospital at 1 site in Denmark.
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 4 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2025. 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 Denmark. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extracellular acidification rate (ECAR) (mpH/min) (time frame: Up to 12 weeks). The study lists 3 primary outcomes in all. 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 NCT05483738, which also lists 31 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 2 Oct 2025.