Bone Mineral Density Loss with Depo Provera (Medroxyprogesterone Acetate)
Depo Provera causes a significant bone mineral density (BMD) loss of approximately 5-6% over 5 years of use, with the most pronounced decline of 2-3% per year occurring during the first two years of treatment. 1
Pattern and Magnitude of BMD Loss
- BMD decreases by approximately 2-3% per year during the first two years of Depo Provera use, with smaller declines in subsequent years 2, 1
- After 5 years of treatment, the mean decreases in BMD are:
- Lumbar spine: -5.38%
- Total hip: -5.16%
- Femoral neck: -6.12% 1
- The decline in BMD is more pronounced during the first two years of use, with the rate of loss slowing to less than 1% per year after this initial period 3, 4
Age-Related Differences in BMD Loss
- Adolescents (12-18 years) experience greater BMD loss than adults:
- Total hip: -6.4% after 240 weeks (4.6 years)
- Femoral neck: -5.4% after 240 weeks
- Lumbar spine: -2.1% after 240 weeks 1
- Women who start Depo Provera before age 20 show approximately 5% BMD deficit at the lumbar spine and hip, while those who start after age 34 do not show significant deficits 5
- Women who begin Depo Provera after age 20 and use it for 15 or fewer years have significantly higher bone density than those who start earlier or use it longer 6
Recovery After Discontinuation
- After discontinuing Depo Provera, there is partial recovery of BMD toward baseline values during the 2-year post-therapy period 1
- BMD increases from 0.3% to 2.0% per year after discontinuation, depending on length of use and bone site 4
- At the spine, BMD increases by approximately 4.9% after discontinuation when switching to non-hormonal contraception 7
- At the femoral neck, BMD increases by approximately 3.2% after discontinuation when switching to non-hormonal contraception 7
- Longer duration of treatment is associated with less complete recovery during the 2-year period following the last injection 1
- Some studies suggest a "rebound phenomenon" where BMD levels may be higher 4-5 years after discontinuation than in non-users 3
Mechanism of BMD Loss
- Depo Provera acts on the skeleton mainly through estrogen deficiency 5
- Users have lower estradiol and higher IGF-1 levels than non-users 5
- Bone turnover is increased in Depo Provera users across all age groups 5
Clinical Implications and Management
- All patients using Depo Provera should be counseled about measures that promote skeletal health:
- Daily intake of 1300 mg of calcium and 600 IU of vitamin D
- Regular weight-bearing exercise 2
- The FDA has issued a black box warning about the risk of decreased BMD among Depo Provera users 2
- Despite initial concerns, the American College of Obstetricians and Gynecologists does not advise limiting Depo Provera use to 2 years or routinely monitoring bone density after that time frame 2
- Risk assessment for osteoporotic fracture may include tools such as FRAX when considering bone-modifying agents 2
The evidence demonstrates that while Depo Provera causes significant BMD loss, particularly in the first two years of use, this loss slows over time and is partially reversible after discontinuation. The clinical impact is most significant for adolescents and young women who have not yet achieved peak bone mass.