Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics

Curr Drug Saf. 2008 Sep;3(3):185-9. doi: 10.2174/157488608785699432.


Many central nervous system active drugs can alter postural balance, increasing the risk of fractures. Anxiolytics and sedatives include the benzodiazepines, and these have been associated with a limited increase in the risk of fractures, even at low doses, probably from an increased risk of falls. No systematic differences have been shown between benzodiazepines with long and short half-lives. Although the increase in risk of fractures was limited, care must still be taken when prescribing for older fall-prone subjects at risk of osteoporosis. Neuroleptics may be associated with a decrease in bone mineral density and a very limited increase in fracture risk. Antidepressants are associated with a dose-dependent increase in the risk of fractures. The increase in relative risk of fractures seems to be larger with selective serotonin reuptake inhibitors (SSRIs) than with tricyclic antidepressants. The reason for this is not known but may be linked to serotonin effects on bone cells and the risk of falls. With the wide use of SSRIs, more research is needed. Lithium is associated with a decrease in the risk of fractures. This may be linked to its effects on the Wnt glycoprotein family, which is a specialised signalling system for certain cell types.

Publication types

  • Review

MeSH terms

  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / therapeutic use
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Central Nervous System Agents / adverse effects*
  • Central Nervous System Agents / therapeutic use
  • Clinical Trials as Topic
  • Fractures, Bone / chemically induced*
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use
  • Lithium Compounds / adverse effects
  • Lithium Compounds / therapeutic use


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Antipsychotic Agents
  • Central Nervous System Agents
  • Hypnotics and Sedatives
  • Lithium Compounds