Bone density and remodeling after discontinuation of sequential therapy for premenopausal idiopathic osteoporosis
Adi Cohen1, Mafo Kamanda-Kosseh2, Ragyie Rawal2
1Columbia University Irving Medical Center, New York, NY, USA. ac1044@columbia.edu.
Abstract:
In premenopausal IOP, BMD gains on teriparatide-denosumab were maintained on bisphosphonate over 1 year. In 19 followed after bisphosphonate, there was a significant bone loss over 6M, leading to retreatment in some. BMD remained significantly above pretreatment baseline. In premenopausal IOP, the optimal duration of bisphosphonate after denosumab requires further study. We have previously reported that sequential teriparatide-denosumab resulted in large BMD increases in premenopausal women with idiopathic osteoporosis (IOP), and that BMD remained stable with bisphosphonate (alendronate or zoledronate) for 1 year after denosumab cessation (Bisphosphonate Extension Study; BES Year 1). To determine the durability of this effect, an observation year (BES Year 2) off therapy was planned.
Participants:
19 women, aged 44 ± 8, with premenopausal IOP.
Measures:
BMD by DXA, serum CTX every 6 months (M).
Results:
On sequential teriparatide-denosumab, BMD increased by 23 ± 9% at the spine and 12 ± 7% at the total hip. In BES Year 1 on bisphosphonate, BMD and CTX did not change significantly at 6M or 12M. From 12-18M of BES Year 2, BMD declined by 4.2 ± 2.5% at the spine and 1.4 ± 2.1% at the total hip (both p < 0.05); other sites remained stable. CTX increased by 218 ± 210 pg/ml (p < 0.05). At 18M, ten participants resumed bisphosphonates because of bone loss or low BMD and nine continued observation. By the end of BES Year 2, spine BMD stabilized in both groups. BMD at the spine and hip was significantly and substantially higher than before beginning teriparatide.
Conclusion:
In premenopausal women with IOP, sequential therapy with teriparatide-denosumab was associated with large gains in bone mass that were maintained by 1 year of bisphosphonate treatment. There was significant bone loss during the first 6 months after discontinuing bisphosphonates, leading to retreatment in about half the participants. Despite this bone loss, BMD remained significantly above pretreatment levels. In premenopausal women with IOP, the optimal duration of bisphosphonate therapy after denosumab cessation requires further study.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03396315.
Related Concept Videos
01:40Bone Remodeling
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:31Osteoclasts in Bone Remodeling
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:25Role of Vitamins in Maintaining Bone Health
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...