They also found a small amount of bone loss (0.5% at the lumbar spine and 1.3% at the femoral neck) in users of very-low-dose OCs (20 μg ethinyl estradiol), compared with a gain of 1.9% at the lumbar spine and 0.6% at the femoral neck in nonusers of hormonal contraception.
Women who made a transition from DMPA to a very-low-dose OC recovered bone mass slowly. After DMPA was discontinued, women who selected nonhormonal contraception recovered BMD (4.9% at the spine, 3.2% at the femoral neck)—unlike those who chose a very-low-dose OC, who regained BMD at the spine (2.3%) but not the femoral neck (–0.7%).
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Use of very-low-dose oral contraception (20 μg ethinyl estradiol) may lead to a small amount of bone loss or failure of bone accretion. Use of depot medroxyprogesterone acetate (DMPA) is associated with a greater degree of bone loss, but this loss is largely reversible at the spine. Use of a 20-μg oral contraceptive (OC) after discontinuation of DMPA may slow bone recovery.
As ACOG has indicated, concerns about skeletal health should not influence the decision to initiate or continue DMPA. Likewise, such concerns should not lead to restrictions on the use of OCs in teens or adult women. However, clinicians may wish to take bone effects into consideration when choosing the estrogen dosage of OCs for women younger than 30 who have yet to attain peak bone mass.
Denosumab nears FDA approval for treatment of osteoporosis
Cummings SR, San Martin J, McClung MR, et al; FREEDOM trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–765.
Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. 2009 [Epub ahead of print].
Miller PD, Bolognese MA, Lewiecki EM, et al, for the Amg Bone Loss Study Group. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008;43:222–229.
An FDA panel advising the Division of Reproductive and Urologic Products voted to approve denosumab (proposed brand name: Prolia) as a treatment for osteoporosis. The drug is a fully human monoclonal antibody to the receptor activator of nuclear factor-B ligand (RANKL), a cytokine that is essential for the formation, function, and survival of osteoclasts. By binding RANKL, denosumab prevents interaction between RANKL and its receptor, RANK, on osteoclasts and osteoclast precursors and thereby inhibits osteoclast-mediated bone resorption. Its effects are reversible.
Trial: Denosumab versus placebo
Cummings and colleagues reported the findings of the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial, which involved 7,868 women 60 to 90 years old who had a BMD T-score between –2.5 and –4.0 at the lumbar spine or total hip. Participants were randomly assigned to receive 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary endpoint was new vertebral fracture. Secondary endpoints included nonvertebral and hip fractures.
Findings included:
- Denosumab reduced the risk of new, radiographically detected vertebral fracture, with a cumulative incidence of 2.3%, versus 7.2% in the placebo group (risk ratio, 0.32; P<.001).
- Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; P=.04).
- Denosumab reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; P=.01).
- There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and no cases of osteonecrosis of the jaw or adverse reaction to injection of the drug.
How does denosumab compare with alendronate?
Kendler and associates explored a clinically relevant question: What are the effects of switching from a bisphosphonate (in this case, alendronate) to denosumab?
They studied 504 postmenopausal women who were at least 55 years old, had a T-score between –2 and –4, and had been taking alendronate for at least 6 months. These women were randomized in double-blinded, double-dummy fashion to 60 mg of subcutaneous denosumab or a continuation of 70 mg of oral alendronate. Follow-up was 12 months.
Findings included:
- Among the women making a transition to denosumab, total hip BMD increased by 1.9% at 12 months, versus 1.05% in women continuing on alendronate (P<.0001).
- Women making a transition to denosumab also gained significantly more BMD at 12 months at the lumbar spine, femoral neck, and the distal third of the radius (all P<.0125).
- The transition to denosumab reduced bone turnover to a greater degree than did continuing alendronate.