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Does Parathyroidectomy increase risk of fracture with primary hyperparathyroidism (PHPT)?

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Primary hyperparathyroidism (PHPT) is an endocrine condition that causes osteoporosis, kidney stones, decreased kidney function, and poor quality of life in older persons. In the US, it affects mostly people over 65, and its frequency has risen over the last three decades.

Patients with symptomatic PHPT should undergo parathyroidectomy, which is the only therapeutic option. As imaging and minimally invasive surgical techniques have improved during the past two decades, guidelines for operative treatment have expanded as well.

However, the vast majority of elderly people with PHPT are monitored nonoperatively, and parathyroidectomy rates have been steadily dropping in this cohort. The lack of high-quality comparative efficacy trials of parathyroidectomy in older adults with PHPT, particularly those in their 70s and 80s, is likely to explain the low utilization of parathyroidectomy.

A higher risk of fractures is linked to primary hyperparathyroidism. Parathyroidectomy improves bone mineral density in randomized clinical trials, whereas nonoperative therapy is associated with a decline in bone mass over time. There is insufficient evidence to say if this translates to a lower risk of fracture in elderly people.

A large observational study of PHPT patients found that parathyroidectomy reduced the risk of fractures when compared to observation or bisphosphonate treatment. However, the operatively managed cohort was much younger than the nonoperatively managed cohort, and the analysis did not account for relevant competing risks. As a result, the data cannot be used to determine therapy decisions for older adults, who make up the majority of PHPT patients.

The goal of this study was to see if parathyroidectomy is linked to a lower risk of clinical fracture in elderly people with PHPT, utilizing approaches that controlled for treatment selection bias and took into consideration the competing risk of death. The researchers also looked at short- and long-term absolute fracture risk reduction, as well as treatment heterogeneity within subgroups of interest, such as those with and without osteoporosis. They anticipated that the benefits of parathyroidectomy in terms of reduced fracture risk would be shown in older people as well, and that a time horizon for benefit from parathyroidectomy might be established to help guide treatment decisions in this group.

From 2006 through 2017, all Medicare beneficiaries with PHPT were included in this population-based, longitudinal cohort research. Two competing risk regression models were used to examine the relationship between parathyroidectomy (parathyroidectomy) and the incidence of fractures in patients.

Among the 210,206 Medicare patients with PHPT (mean [SD] age 75 [6.8] years; 165,637 [78.8 percent] females; 183,433 [87.3 percent] White individuals), 63,136 (30.0 percent) underwent parathyroidectomy within one year of diagnosis, and 147,070 (70.0 percent) were treated nonoperatively. The unadjusted incidence of fracture was 10.2 percent in patients treated with parathyroidectomy over a mean (SD) follow-up period of 58.5 (35.5) months. During a mean (SD) follow-up of 52.5 (33.8) months, the unadjusted fracture rate in patients observed nonoperatively was 13.7 percent.

On multivariable analysis, parathyroidectomy was linked to decreased adjusted rates of any fracture (hazard ratio [HR], 0.78; 95 percent confidence interval [CI], 0.76-0.80) and hip fracture (hazard ratio [HR], 0.78; 95 percent confidence interval [CI], 0.76-0.80). (HR, 0.76; 95 percent CI, 0.72-0.79). When compared to nonoperative therapy, parathyroidectomy was related with adjusted absolute fracture risk reductions of 1.2 percent (95 percent CI, 1.0–1.4), 2.8 percent (95 percent CI, 2.5–3.1), and 5.1 percent (95 percent CI, 4.6–5.5) at 2, 5, and 10 years, respectively. There were no significant variations in the association of parathyroidectomy with fracture risk by age group, sex, frailty, history of osteoporosis, or compliance with operative guidelines when subgroup analysis was performed.

When the competing risk of mortality was taken into consideration, Fine-Grey competing risk regression revealed that parathyroidectomy was related with a decreased risk of any fracture and hip fracture (HR, 0.84; 95 percent CI, 0.82-0.85; and HR, 0.83; 95 percent CI, 0.80-0.85, respectively).

This longitudinal cohort analysis concluded that parathyroidectomy was linked with a reduced risk of fracture in general and hip fracture in older persons with PHPT, implying a clinically relevant advantage of surgical therapy in this population.

Source: doi:10.1001/jamainternmed.2021.6437

Image Credit: Getty

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