Safety Assessment Among Women With Postmenopausal Osteoporosis and Men With Osteoporosis in Multiple Observational Databases

Inclusion Criteria for women with postmenopausal osteoporosis:

- Postmenopausal women: Postmenopausal status will be determined based on age and
defined as women ≥ 55 years old. For the Medicare database, only women ≥ 65 years old
will be included in the analysis, given that generally all individuals in the US ≥ 65
years old are eligible for Medicare coverage and data on postmenopausal women less
than 65 years old will be available for only a small number of women meeting other
specialized eligibility criteria.

- Women with Post Menopausal Osteoporosis: The presence of Post Menopausal Osteoporosis
will be determined utilizing an algorithm based upon definition of postmenopausal
women (≥ 65 years old in Medicare or ≥ 55 years old in other data systems),
diagnostic codes indicating osteoporosis, diagnostic codes indicating osteoporotic
fracture, and/or relevant postmenopausal osteoporosis treatment codes.

Exclusion Criteria for women with postmenopausal osteoporosis:

• Women with postmenopausal osteoporosis: Women with Paget's disease during the 12-month
period prior to meeting criteria for inclusion in postmenopausal osteoporosis population
will be excluded. Additionally, in US Medicare and United Healthcare, women with a
diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment with
chemotherapy, hormonal therapy or radiation therapy for cancer up to 12-months before
index date will be excluded. In the Scandinavian national registries, women with a
diagnosis of cancer according to the patient registry and/or cancer registry up to
12-months prior to meeting criteria for inclusion in postmenopausal osteoporosis
population will be excluded.

Inclusion criteria for men with osteoporosis:

- Men ≥ 65 years old in the Medicare database or ≥ 30 years old in United Healthcare
who receive at least one denosumab 60 mg injection will be included. All men need to
be continuously enrolled for at least 12 months prior to start of follow-up. A
diagnosis code of osteoporosis or osteoporotic fracture would not be required because
it is known that male osteoporosis is under-diagnosed. The exclusion of patients with
cancer or Paget disease (as described in the Exclusion Criteria Section) will ensure
that patients treated with Prolia is for osteoporosis but not for other indications.
The index date is defined as the date when a patient first satisfies all inclusion
criteria.

Exclusion Criteria for men with osteporosis:

- Men with a diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment
with chemotherapy, hormonal therapy or radiation therapy for cancer up to 12 months
before the index date will be excluded.

- Men with Paget's disease during the 12-month period prior to the index date will also
be excluded.