Influence of denosumab on bone mineral density in a severe case of pregnancy-associated osteoporosis

Abstract

Pregnancy and lactation-associated osteoporosis (PLO) with predominantly subsequent vertebral fracture is a rare but severe disease with an estimated incidence of 0.4 in 100,000. In the past, patients with PLO have been predominantly treated with oral and i.v. bisphosphonates to reduce subsequent fracture risk. Hereby, the use of bisphosphonates in premenopausal women is controversial, as bisphosphonates know to persist in bone for many years and can be exposed and circulate in maternal serum and subsequently pass the placenta barrier and may have a detrimental effect on fetal bone health. Here we report the effects of denosumab on the bone mineral density (BMD) and subsequent fracture risk in PLO. In this case presentation, denosumab was administered postpartum with 3000 IE vitamin D and 1000 mg of calcium daily in a patient with PLO and vertebral fracture of L1 and L4. After 18 months of treatment with denosumab, we could demonstrate a clinical significant increase of BMD at the lumbar spine, femoral neck, and total hip of 32.2%, 13.0%, and 11.5% respectively with no further subsequent fractures. As the patient had regular menstrual cycles and considered a further pregnancy, denosumab treatment was terminated and soon a second pregnancy occurred. After the second pregnancy, BMD decreased at the lumbar spine, femur neck, and total hip by −8.8%, −6.9%, and −7.0% respectively compared to the maximum values during treatment with denosumab, but was still significantly higher compared to baseline levels with no further fractures.

Pregnancy and Lactation-Associated Osteoporosis Successfully Treated with Romosozumab: A Case Report

“…PLO was first described in 1955 by Nordin and Roper [ 15 ]. Its incidence is estimated to be 4–8 cases per 1,000,000 women [ 8 , 16 ], but the precise incidence is probably higher due to undiagnosed cases. Back pain caused by a vertebral fracture is one of the most common symptoms of PLO, and more than two-thirds of the vertebral fractures in cases of PLO occur in a first pregnancy [ 2 , 17 ].…”

“…The mean half-life of 60 mg denosumab is 25.4 days, and its concentration declines over a period of 4–5 months. Stumpf et al (2021) reported the case of a patient with PLO treated with denosumab along with calcium and vitamin D supplementation, which led to increases in BMD at the lumbar spine, femoral neck, and total hip by 21.2%, 5.6%, and 8.0% at 12 months and by 32.0%, 13.0%, and 11.5% at 18 months, respectively [ 8 ]. Another patient with PLO was treated with weekly teriparatide (56.5 μg/week) for 6 weeks, followed by denosumab (60 mg) for 6 months, and at 12 months, she exhibited increases in BMD from baseline at the lumbar spine (L2–L4) and femoral neck by 16.5% and 3.9%, respectively [ 9 ].…”

“…Teriparatide is an osteoanabolic agent and does not accumulate in the bone. Many reports of the BMD increase effect of teriparatide for the treatment of PLO were publicized [ 8 , 9 , 10 , 11 , 12 , 23 , 29 , 30 , 31 ]. Teriparatide effectively improved the lumbar BMD values of PLO patients by almost 20% at 12 months [ 11 , 29 ] and by 19–36% at 18 months [ 10 , 30 , 31 ].…”

“…A common first step in the treatment of a patient with PLO is delactation with supplementation of calcium with or without vitamin D [ 1 ]. Various drugs were reported as treatment for PLO, including bisphosphonate [ 2 , 4 , 5 ], strontium ranelate (SrRan) [ 6 , 7 ], denosumab [ 8 , 9 ], and teriparatide [ 10 , 11 , 12 ]. Monoclonal antibody romosozumab, a sclerostin inhibitor, is one of the key drugs used to treat postmenopausal osteoporosis [ 13 , 14 ], but our search revealed no report of a patient with PLO treated with romosozumab.…”

Pregnancy and lactation-associated osteoporosis in a Systemic Lupus Erythematosus patient

“…1 PLO is a rare disease that occurs more frequently in primiparous women over 30 years of age, with most cases occurring during the third trimester of pregnancy or in the early postpartum period. 1,3,4 Severe and prolonged back pain is the most frequent complaint and results from the presence of vertebral fractures. 1,4 The development of PLO can be explained by changes in calcium metabolism that occur in pregnancy.…”