Diagnosing OP starts with a thorough history and physical, and should include documentation of risk factors as well as accurate height (or loss of height) and weight to calculate BMI. (◘ Table 10.1)

BMD is measured standardly by dual energy absorptiometry (DXA); however assessing bone quality is more complex. Bone microarchitecture can be evaluated with high resolution quantitative computed tomography (QCT) [9], high resolution magnetic resonance imaging (MRI) [10], or double tetracycline-labeled transiliac bone biopsy with histomorphometry, but these are not commonly used in clinical practice [11].

A DXA study calculates both a T– and Z-score and provides these to the clinician for interpretation. The T-score is a range based on standard deviations (SD) below that of a young adult at peak bone density, which is used as the reference population, which is unique to the actual DXA scanner. In contrast, the Z-score refers to a BMD that uses an age matched reference population. Specific BMD based cutoffs as defined by the WHO for a diagnosis of OP are outlined in ◘ Table 10.2 [12].

As BMD is a surrogate marker of bone strength and there are many other factors that contribute, a diagnosis of clinical osteoporosis is made regardless of the BMD result in the setting of a fragility fracture. Osteoporotic fragility fractures are those occurring from a fall or less than standing height, occurring separately from any trauma such as a motor vehicle accident or other major trauma (excluding toes, nose, and fingers), regardless of T– and Z-score. This is especially important as many women and providers often mistake fractures obtained from a slip and fall as expected rather than recognizing the pathological nature which requires further investigation and treatment.

Screening all women with a DXA starts at age 65, unless a woman meets criteria for having known risk factors and/or a low bone density result might influence a woman’s decision to initiate hormonal therapy for other menopausal symptoms [13]. In premenopausal women and women under the age of 50 who are not yet menopausal, race-adjusted Z-scores should be used when interpreting the DXA. For postmenopausal women, the T-score is used.

Secondary osteoporosis is OP caused by another condition or medication and may go undetected as there are numerous potential causes, several of which are somewhat obscure (◘ Table 10.3).

Approximately half of premenopausal women with OP and one-fifth of postmenopausal women have a secondary cause [14]. A cursory evaluation should thus be completed for all patients with OP before proceeding to treatment, tailored further by the patients’ history and physical. Secondary causes should also be revisited in patients who lose bone density and/or fracture despite therapy [15]. Although there is not 100% consensus amongst the many organizations that have guidelines on OP as to precisely what an initial evaluation should entail, most include those in ◘ Table 10.4. When Z-scores are low, one should especially consider evaluating for secondary causes of OP (◘ Table 10.5).

Additional pharmacologic therapy is indicated in all patients with OP, diagnosed either by BMD or clinically by presence of a fragility fracture [12]. For those with low bone density, the Fracture Risk Assessment Tool (FRAX^®) is utilized to calculate absolute 10 year fracture risk. Based off of cost benefit analysis, if the calculated 10 year risk of a hip fracture is greater than or equal to 3%, or if any major osteoporotic-related fracture probability is equal to or greater than 20%, then the patient should be started on treatment after excluding and/or treating secondary causes of OP. The FRAX^® calculation considers the patient’s femoral neck bone mineral density and personalized risk factors. FRAX calculation takes into account the patient’s femoral neck bone mineral density, (not vertebral measurement) and personalized risk factors, which include the patient’s age, sex, BMI, personal history of prior fracture, family history of an osteoporotic fracture, smoking status, personal history of glucocorticoid use (>5 mg/day or longer than 3 months in a lifetime), rheumatoid arthritis, or other diagnosis of secondary osteoporosis, and alcohol intake. FRAX^® scores can quickly be calculated using an online tool: [► http://​www.​shef.​ac.​uk/​FRAX]

FRAX^® is to be used as a guideline, and clinical consideration should still be utilized, especially as several limitations exist [16]. First, the FRAX^® calculation only uses the femoral neck BMD, which can underestimate risk in patients who have low lumbar spine but normal femoral neck measurement, a common scenario in the early years following menopause. Also, only dichotomous yes/no responses are allowed for smoking, alcohol and steroid use, despite it being well known that higher doses and longer durations of these can disproportionately impact bone strength. Also, no consideration is given to fall risk, which is a significant fracture risk. Fall history is included in the Asian Garvan fracture risk calculator, an alternative to FRAX^® [17].

Universal recommendations for all patients with OP and low bone density include weight bearing exercise to increase bone density and muscle strength. Mechanical loading through exercise increases bone mass [18], while immobility is strongly correlated with declining bone density [19, 20]. Assessing for fall assessment and prevention (vision, home safety, balance training and physical therapy) becomes more critical as the woman advances into the geriatric years [20]. Smoking should be eliminated [21] and alcohol intake limited to <14 drinks/week in women (1 drink = 1.5 fl oz. spirits or 5 fl oz. of wine or 12 fl oz. beer) [22]. All women should maintain adequate intake and serum levels of vitamin D, which is difficult to obtain adequately from the diet so supplementation is usually needed (vit d3 800–1000 IU/day in most and higher doses required in some women) [23, 24, 25].

All women should be advised to ingest adequate daily calcium in their diet and likewise to obtain adequate levels of vitamin D. The recommended daily intake of calcium is 1000 mg for premenopausal women and 1200 mg for postmenopausal women daily [26] and is optimally obtained from dietary sources such as dairy (low-fat milk, cheese, and yogurt), salmon, tofu, broccoli, almond milk, and some fortified cereals. Calcium supplements should be added only when an intake of 1200 mg daily in the diet is not obtainable. Some studies have suggested that calcium supplementation may increase cardiovascular risk [27]. These have been variable and the data remains unclear. As calcium is readily available from a variety of dietary sources, it is encouraged to reach daily recommended intake levels through diet when possible.

Estrogen decreases osteoclast activity and stimulates osteoclast apoptosis. It also functions to block RANK-L by inhibiting TNF-alpha. In the 5–7 years following the onset of menopause, with reductions of estrogen, women can lose up to 20% of their bone mass, primarily of cancellous bone (i.e., spine and calcaneus) [28]. In the Women’s Health Initiative (WHI), hormone therapy (HT) reduced the risk of hip fracture by 50%. In the estrogen only arm, fracture reduction was seen at all sites [28]. In both the estrogen (ET) and the estrogen + medroxyprogesterone acetate (MPA) treatment arms (EPT), hip fractures were reduced compared to placebo [29]. Post hoc analysis of the WHI has showed additional benefits, particularly for women within 10 years of menopause, now referred to as the timing hypothesis. An apparent reduction in the risk of cardiovascular events was seen in this group of women who used HT within the first 10 years of menopause onset [30]. HT in both arms decreased the risk of colon cancer and diabetes. Furthermore, women in the estrogen only arm had no increased risk of breast cancer compared to placebo. The increased risk of breast cancer in the EPT arm seemed to increase significantly after 5 years of therapy [31].

HT increased stroke risk after 3 years of therapy in both arms; however, the increased absolute risk with EPT was only 3 additional strokes per 10,000 women per year of therapy in those within 5 years of menopause and 6 within 10 years of menopause [32]. The ET arm showed an increased risk only in women age 60 and over. All of these absolute risks are actually defined as rare events by the WHO criteria [33].

Estrogen is also the most efficacious treatment option for postmenopausal women suffering from severe vasomotor symptoms (VMS), which are experienced by upwards of 60–90% of women, of which nearly a quarter of women report these symptoms as unbearable [34]. Therefore, estrogen may be ideal in women in the first 5 years postmenopausally without significant risks for stroke or breast cancer that have low BMD and are also seeking relief of concomitant VMS and genitourinary syndrome of menopause (GSM). Estrogen has a dose dependent effect on bone and its effects are lost with cessation of therapy.

In postmenopausal women ages 60–80 who have osteopenia but are without other symptoms of menopause that require systemic hormonal therapy, ultra-low dose transdermal estradiol (Menostar^®) can be used for the prevention of OP. Due to the relatively low dose of estrogen, only twice annual progestin is needed for women with a uterus.

Bisphosphonates (BPS) are anti-resorptive medications that activate osteoclasts. BPS have many advantages being overall very safe, effective, affordable, and are available in a variety of formulations. Many formulations exist, but no head-to-head studies are available. Multiple large meta-analyses have concluded that the four available BPS—alendronate, risedronate, ibandronate, and zoledronic acid— reduce fractures in postmenopausal women compared to placebo, but ibandronate does not have data showing reductions in hip fracture or non-vertebral fractures [35]. Before starting treatment, vitamin D deficiency and hypocalcemia (both of which are common in patients post gastric bypass) [36] should be corrected. Serum creatinine should be measured as BPS are contraindicated with a creatinine clearance of less than or equal to 35 mL/min. [37] (◘ Table 10.6).