How do the nerve-pain drugs gabapentin and pregabalin affect bone, muscle and cartilage — and what does that mean for physical rehabilitation?
Gabapentin, a review (Current Osteoporosis Reports 2022, PMID 36149592) — the same α2δ1 subunit is expressed in bone, muscle and cartilage, where it has important roles in skeletal formation, mechanosensation and normal tissue function and repair. No numeric effect size is reported for Gabapentin in the source abstract.
Source: Current Osteoporosis Reports 2022, PMID 36149592 ↗ · Research map · How Magellan grades evidence · evidence confidence: low
Current Osteoporosis Reports · 2022 · PMID 36149592 · DOI 10.1007/s11914-022-00750-x
Gabapentin and pregabalin relieve nerve pain by blocking the α2δ1 calcium-channel subunit — but that same subunit matters in bone, muscle and cartilage, so long-term use is linked to worse musculoskeletal outcomes and higher fracture risk: a key consideration in physiatry and rehab.
The question
How do the nerve-pain drugs gabapentin and pregabalin affect bone, muscle and cartilage — and what does that mean for physical rehabilitation?
What they tested
Because gabapentinoids act on the α2δ1 calcium-channel subunit that is also expressed in musculoskeletal tissues, long-term use may disrupt the calcium-mediated signaling important for skeletal formation, mechanosensation and tissue repair.
How they did it
A narrative review of the mechanism of action of gabapentinoids and the evidence on how chronic treatment affects the musculoskeletal system.
What they found
Gabapentin (GBP) and pregabalin (PGB), originally antiepileptics and now first-line for neuropathic pain (and often prescribed off-label for migraine and back pain), produce analgesia by selectively binding the α2δ1 auxiliary subunit of voltage-sensitive calcium channels and inhibiting channel function. The same α2δ1 subunit is expressed in bone, muscle and cartilage, where it has important roles in skeletal formation, mechanosensation and normal tissue function and repair. Long-term gabapentinoid use is associated with detrimental musculoskeletal outcomes, including increased fracture risk.
What it means
Clinicians guiding rehabilitation should weigh the potential musculoskeletal complications of chronic gabapentinoid use, since these drugs may interfere with the calcium signaling that bone, muscle and cartilage rely on to adapt and heal.
Limitations
Much of the mechanistic evidence comes from preclinical and tissue-level studies; the authors call for more research to define the clinical magnitude of the musculoskeletal risk.
The paper at a glance
| Title | Effects of Gabapentin and Pregabalin on Calcium Homeostasis: Implications for Physical Rehabilitation of Musculoskeletal Tissues |
|---|---|
| Journal | Current Osteoporosis Reports |
| Year | 2022 |
| PMID | 36149592 ↗ |
| DOI | 10.1007/s11914-022-00750-x ↗ |
| Topic | Pain, nerves & musculoskeletal medicine |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). How do the nerve-pain drugs gabapentin and pregabalin affect bone, muscle and cartilage — and what does that mean for physical rehabilitation? [Plain-English summary of Current Osteoporosis Reports 2022, PMID 36149592, DOI 10.1007/s11914-022-00750-x]. Magellan Longevity. https://magellanlongevity.com/study/gabapentinoid_msk_calcium.html@misc{magellan_gabapentinoid_msk_calcium,
title = {How do the nerve-pain drugs gabapentin and pregabalin affect bone, muscle and cartilage — and what does that mean for physical rehabilitation?},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/gabapentinoid_msk_calcium.html}},
note = {Plain-English summary of PubMed PMID 36149592; DOI 10.1007/s11914-022-00750-x; Current Osteoporosis Reports 2022. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
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