Anti-sclerostin antibodies and abaloparatide have additive effects when used as a countermeasure against disuse osteopenia in female rats.

Brent MB, Brüel A, Thomsen JS

Bone7 Apr 2022Cited by 11 (Europe PMC)

PMID35398589DOI10.1016/j.bone.2022.116417PepBankPUB-35398589

Publisher page PubMedAsk about this study

Summary

Prolonged disuse and substantial mechanical unloading are particularly damaging to skeletal integrity. Preclinical studies in rodents and clinical studies have highlighted the need for potent bone anabolic drugs to counteract disuse-induced osteopenia. The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model. Eighty female Wistar rats were divided into the following six groups: 1. Baseline (n = 12); 2. Control (Ctrl) (n = 12); 3. BTX (n = 12); 4. BTX + Scl-Ab (n = 16); 5. BTX + ABL (n = 12); and 6. BTX + Scl-Ab + ABL (n = 16). Disuse was achieved by injecting 4 IU BTX into the hind limb musculature at study start. Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks. Hind limb disuse dramatically decreased muscle mass and skeletal integrity and deteriorated the cortical morphology and trabecular microstructure. Treatment with Scl-Ab alone prevented most of the adverse cortical and trabecular effects of disuse, while ABL monotherapy mainly attenuated the disuse-induced loss of femoral areal bone mineral density (aBMD). Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively. The potent and additive osteoanabolic effect of Scl-Ab and ABL, when given in combination, is highly intriguing and underlines that an osteoanabolic bone gain can be maximized by utilizing two pharmaceuticals targeting different cellular signaling pathways. From a clinical perspective, a combination treatment may be warranted in patients where the osteoanabolic effect of either monotherapy is not sufficient, or if a dose-reduction is required due to adverse effects.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

4 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In rats with disuse, adding abaloparatide to Scl-Ab increased aBMD by 10% versus Scl-Ab alone.
In plain wordsIn rats with disuse, adding abaloparatide increased bone density more than Scl-Ab alone.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseAreal BMD with combination versus Scl-Ab
Study
ratn = 32
Female Wistar rats with botulinum toxin-induced hind limb disuse
Comparator
Scl-Ab monotherapy
Outcome group
Bone and joint · Musculoskeletal
Studied dose
80 μg/kg five days a week · subcutaneous · four weeksAs given in this study (rat).
Source sentences
Summary
Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model.
Summary · context
Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks.
Show in the study text Report a problemFND-3539858902
02AnimalAnimal study (in vivo)Efficacy outcome
In rats with disuse, adding abaloparatide to Scl-Ab increased epiphyseal trabecular BV/TV by 25% versus Scl-Ab alone.
In plain wordsIn rats with disuse, adding abaloparatide increased epiphyseal trabecular bone volume more than Scl-Ab alone.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseEpiphyseal trabecular BV/TV versus Scl-Ab
Study
ratn = 32
Female Wistar rats with botulinum toxin-induced hind limb disuse
Comparator
Scl-Ab monotherapy
Outcome group
Bone and joint · Musculoskeletal
Studied dose
80 μg/kg five days a week · subcutaneous · four weeksAs given in this study (rat).
Source sentences
Summary
Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model.
Summary · context
Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks.
Show in the study text Report a problemFND-3539858904
03AnimalAnimal study (in vivo)Efficacy outcome
In rats with disuse, adding abaloparatide to Scl-Ab increased metaphyseal bone strength by 18% versus Scl-Ab alone.
In plain wordsIn rats with disuse, adding abaloparatide increased metaphyseal bone strength more than Scl-Ab alone.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseMetaphyseal bone strength versus Scl-Ab
Study
ratn = 32
Female Wistar rats with botulinum toxin-induced hind limb disuse
Comparator
Scl-Ab monotherapy
Outcome group
Bone and joint · Musculoskeletal
Studied dose
80 μg/kg five days a week · subcutaneous · four weeksAs given in this study (rat).
Source sentences
Summary
Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model.
Summary · context
Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks.
Show in the study text Report a problemFND-3539858906
04AnimalAnimal study (in vivo)Efficacy outcome
In rats with hind limb disuse, abaloparatide monotherapy attenuated femoral areal BMD loss.
In plain wordsIn rats with hind limb disuse, abaloparatide reduced femoral bone density loss compared with untreated disuse.
Peptide
Abaloparatide (Tymlos)
Outcome
DecreaseFemoral areal BMD loss
Study
ratn = 24
Female Wistar rats with botulinum toxin-induced hind limb disuse
Comparator
Disuse without treatment
Outcome group
Bone and joint · Musculoskeletal
Studied dose
80 μg/kg five days a week · subcutaneous · four weeksAs given in this study (rat).
Source sentences
Summary
Treatment with Scl-Ab alone prevented most of the adverse cortical and trabecular effects of disuse, while ABL monotherapy mainly attenuated the disuse-induced loss of femoral areal bone mineral density (aBMD).
2 context sentences(design, population, supporting numbers)
Summary · context
The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model.
Summary · context
Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks.
Show in the study text Report a problemFND-3539858901

Studies that did not test the peptide alone3

In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Abaloparatide (Tymlos).

05AnimalNot a test of Abaloparatide (Tymlos) aloneAnimal study (in vivo)Efficacy outcome
In rats with disuse, Scl-Ab plus abaloparatide increased aBMD by 20% versus abaloparatide alone.
In plain wordsIn rats with disuse, Scl-Ab plus abaloparatide increased bone density more than abaloparatide alone.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseAreal BMD with combination versus ABL
Study
ratn = 28
Female Wistar rats with botulinum toxin-induced hind limb disuse
Comparator
Abaloparatide monotherapy
Outcome group
Bone and joint · Musculoskeletal
Source sentences
Summary
Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model.
Summary · context
Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-3539858903
06AnimalNot a test of Abaloparatide (Tymlos) aloneAnimal study (in vivo)Efficacy outcome
In rats with disuse, Scl-Ab plus abaloparatide increased epiphyseal trabecular BV/TV by 73% versus abaloparatide alone.
In plain wordsIn rats with disuse, Scl-Ab plus abaloparatide increased epiphyseal trabecular bone volume more than abaloparatide alone.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseEpiphyseal trabecular BV/TV versus ABL
Study
ratn = 28
Female Wistar rats with botulinum toxin-induced hind limb disuse
Comparator
Abaloparatide monotherapy
Outcome group
Bone and joint · Musculoskeletal
Source sentences
Summary
Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model.
Summary · context
Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-3539858905
07AnimalNot a test of Abaloparatide (Tymlos) aloneAnimal study (in vivo)Efficacy outcome
In rats with disuse, Scl-Ab plus abaloparatide increased metaphyseal bone strength by 30% versus abaloparatide alone.
In plain wordsIn rats with disuse, Scl-Ab plus abaloparatide increased metaphyseal bone strength more than abaloparatide alone.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseMetaphyseal bone strength versus ABL
Study
ratn = 28
Female Wistar rats with botulinum toxin-induced hind limb disuse
Comparator
Abaloparatide monotherapy
Outcome group
Bone and joint · Musculoskeletal
Source sentences
Summary
Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model.
Summary · context
Scl-Ab (25 mg/kg) was injected s.c. twice weekly, while ABL (80 μg/kg) was injected s.c. five days a week for four weeks.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-3539858907

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:25 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

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