Rapidly Progressive Aortic Stenosis After Teriparatide Initiation: A Rare Case

Introduction:
Recombinant Parathyroid Hormone (rPTH) or Teriparatide is frequently used to manage severe osteoporosis due to its anabolic mode of action particularly in patients who are at a high risk of vertebral and non-vertebral fractures. Aortic valve stenosis is a common valve condition seen in the older population. There are multiple etiologies for aortic stenosis, but drug induced aortic stenosis is rare. Moreover, its natural history includes gradual progression towards severity. We present an interesting case of rapidly progressive aortic stenosis after teriparatide initiation.

Case Description:
An 84-year-old female with history of hypertension, hyperlipidemia, atrial fibrillation presented to the endocrine clinic for management of osteoporosis. She was diagnosed with osteoporosis in 2000 at age 62. Initial etiology was assumed to be post-menopausal and was treated with oral bisphosphonates. As she had compression fractures of her spine while on treatment, secondary causes of osteoporosis were explored, and she was found to have primary hyperparathyroidism. Her labs were significant for PTH-84 pg/ml, Ca-10.8 mg/dl. She underwent parathyroidectomy in 2016 with normalization of PTH and calcium. After her surgery, she was treated with denosumab infusions every 6 months. She did well till June 2021. Her bone mineral density scores were stable throughout this period. At this point, she suffered bilateral atypical femoral fractures and was thought to be due to chronic anti-resorptive therapy. We stopped denosumab and transitioned her to teriparatide daily injections. She did well for 1 year but then presented to us for management in Aug 2022 prior to valve replacement for severe aortic stenosis. Her labs were significant for normal calcium, 25-hydroxy vitamin D and phosphorus levels. On reviewing her echocardiograms prior to and after initiation of teriparatide we found a rapid progression of her aortic stenosis from moderate to severe, based on mean gradients and peak velocities, over a span of 7 months.

Discussion:
Natural progression of aortic stenosis from mild to severe happens over several years (mean duration-5 years), not just a few months. One possible explanation for this rapid progression seen in our patient is due to the presence of osteoblast like cells (arising from vascular endothelial cell precursor cells) in the aortic valve which appear to be stimulated by PTH and hence valve calcification/stenosis. On a thorough review of literature there were no clinical studies that have reported aortic stenosis progression from teriparatide use. To our knowledge, there was a single case report that reported the same phenomenon in Israel. As a result, we wanted to educate the community about the possible association between teriparatide use and worsening aortic stenosis in certain cases. Performing serial echocardiograms in high-risk patients and involving cardiology for early diagnosis and management is essential.