Table 2.
BMD and Fracture Outcomes in Studies Investigating Anti‐Osteoporosis Therapy Exclusively in Premenopausal Women and/or Men Aged <50 Years: Studies of Subjects with IOP and Some Primary and Secondary Etiologies
| Authors | Year | Title | Population | Study design | Intervention and comparator | Follow‐up | Outcome | |
|---|---|---|---|---|---|---|---|---|
| BMD outcomes | Fracture outcomes | |||||||
| AN | ||||||||
| Miller and colleagues 137 | 2004 | Effects of risedronate on bone density in anorexia nervosa | 10 women with AN, compared to published data on 14 controls | Pre‐test post‐test clinical trial | Risedronate 5 mg daily | 9 months | +4.1 ± 1.6% change in spinal BMD in women receiving risedronate versus −1.5 ± 1.0% in controls at 6 months and 4.9 ± 1.0 (risedronate) versus −1.0 ± 1.3 at 9 months (p = 0.03). No increase in hip BMD. | – |
| Miller and colleagues( 67 ) | 2011 | Effects of risedronate and low‐dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo‐controlled study | 77 women with AN | RCT | Risedronate 35 mg weekly + placebo patch versus testosterone 150 μg daily patch + weekly placebo pill versus risedronate 35 mg weekly + testosterone 150 μg daily patch versus double placebo for 12 months | 12 months (study duration) | 3.2% (95% CI 1.8, 4.6%; p < 0.0001) increase in spinal and 1.9% (95% CI 0.4, 3.4%; p = 0.013) BMD with risedronate compared with placebo, over 12 months. No significant effect noted with testosterone treatment | – |
| Resulaj and colleagues( 66 )l | 2020 | Transdermal estrogen in women with anorexia nervosa: an exploratory pilot study | 11 premenopausal, amenorrheic women with AN | Pre‐test post‐test interventional (pilot study) | Transdermal estradiol (0.045 mg/day) and the progestin levonorgestrel (0.015 mg/day) weekly patch | 6 months | Increased spinal BMD (2.0% ± 0.8%; p = 0.033) at 6 months. No change at the total hip or femoral neck. | – |
| Milos and colleagues 138 | 2021 | Positive effect of teriparatide on areal bone mineral density in young women with anorexia nervosa: a pilot study | 10 women aged 18–35 years with AN and BMD Z/T‐score < −2.5 or fragility fracture and Z/T‐score < −1.5 | Pre‐test post‐test interventional study (pilot study) | TPTD 20 μg subcutaneous for 24 months | 24 months | Spinal BMD increased 13.5%, femoral neck BMD increased 5.0% and total hip 4.0%. | – |
| GIO | ||||||||
| Fujita and colleagues 139 | 2000 | Acute alteration in bone mineral density and biochemical markers for bone metabolism in nephrotic patients receiving high‐dose glucocorticoid and one‐cycle etidronate therapy | Patients (mean age 43.0 ± 15.7 years) with nephrotic syndrome exposed to glucocorticoids for >12 months, with spinal BMD <89% of YAM | Pre‐test post‐test interventional study | Etidronate versus no treatment | 3 months | Improvement in spinal BMD with etidronate therapy (9 ± 8%, p = 0.003) | – |
| Lambrinoudaki and colleagues( 29 ) | 2000 | Effect of calcitriol on bone mineral density in premenopausal Chinese women taking chronic steroid therapy: a randomized, double‐blind, placebo‐controlled study | 81 Chinese premenopausal women with SLE, receiving glucocorticoids | RCT | 0.5 μg calcitriol and 1200 mg calcium daily versus 1200 mg calcium and placebo calcitriol versus both placebo calcitriol and placebo calcium | 2 years | 2.1 ± 2.4% increase in spinal BMD in the intervention group compared to baseline value (p < 0.05), but nonsignificant when compared to calcium or placebo groups (0.4 ± 2.9% and 0.3 ± 3.5%, respectively). No significant changes were observed in any treatment group in BMD at the hip or radius. | – |
| Sato and colleagues 140 | 2003 | Effect of intermittent cyclical etidronate therapy on corticosteroid induced osteoporosis in Japanese patients with connective tissue disease: 3 year follow‐up | 21–73‐year‐old adults with underlying connective tissue disease, taking >7.5 mg daily prednisolone for at least 90 days; (subgroup analysis for premenopausal women provided) | RCT | Etidronate disodium (200 mg/day for 2 weeks with 3.0 g calcium lactate and 0.75 μg alphacalcidol daily for 90 days versus 3.0 g calcium lactate and 0.75 μg alphacalcidiol daily for 90 days. | 3 years | Increase in spinal BMD with etidronate versus control: +3.8 ± 6.6% versus −0.2 ± 4.8% (p < 0.01) | Not available for subgroups |
| Nakayamada and colleagues 141 | 2004 | Etidronate prevents high‐dose glucocorticoid induced bone loss in premenopausal individuals with systemic autoimmune diseases | 16 premenopausal women and 5 men with newly diagnosed autoimmune disease and prescribed high‐dose glucocorticoids | RCT | Alfacalcidiol 1 μg/day (n = 11) versus alfacalcidiol and cyclical etidronate (200 mg/day for 14 days) given for 4 cycles, over 12 months | 12 months | Femoral neck BMD increased 2.3 ± 1.5% in the combined group and decreased 2.5 ± 2.4% in the alfacalcidol group, p < 0.05 | – |
| Nzeusseu Toukap and colleagues 142 | 2005 | Oral pamidronate prevents high‐dose glucocorticoid‐induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients | Premenopausal women with connective tissue disease given high‐dose glucocorticoids | RCT | Calcium (500 mg of elemental calcium/day) + vitamin D3 (25,000 units/ month) versus pamidronate (n = 16) 100 mg/day + calcium + vitamin D3 | 12 months | Reduced spinal BMD in controls (−0.045 g/cm2) but not in patients treated with pamidronate (−0.018 g/cm2) at 12 months; reduced BMD at the total hip in controls (−0.033 g/cm2) and in patients receiving pamidronate (−0.017 g/cm2) | – |
| Okada and colleagues 143 | 2008 | Alendronate protects premenopausal women from bone loss and fracture associated with high‐dose glucocorticoid therapy | 47 premenopausal women commencing high dose glucocorticoid therapy for systemic autoimmune diseases | RCT | 1 mg/kg/day prednisolone and alfacalcidol 1 μg/day alone (n = 22) versus prednisolone and alfacalcidol 1 μg/day with alendronate 5 mg/day (n = 25), each for 18 months. | 18 months (completion of treatment) | Spinal BMD change +1.7% ± 1.4% in the combined group and −9.9% ± 1.9% in the alfacalcidol group at 12 months (p < 0.05). Difference also observed at 6 and 18 months. | 4VF in the alfacalcidiol only group between 12–18 months |
| Yeap and colleagues 25 | 2008 | A comparison of calcium, calcitriol, and alendronate in corticosteroid‐treated premenopausal patients with systemic lupus erythematosus | Premenopausal women with SLE receiving glucocorticoids | RCT | Calcium carbonate 500 mg bd (calcium alone), calcitriol 0.25 μg bd plus calcium carbonate 500 mg bd (calcitriol + calcium), and alendronate 70 mg/week plus calcium carbonate 500 mg bd (alendronate + calcium). | 2 years | Alendronate + calcium group showed significant increases in BMD of 2.69% (p < 0.001) in the lumbar spine and 1.41% (p < 0.001) in total hip. There was a 0.93% (p < 0.001) reduction in total hip BMD in the calcium‐alone group; there were no other significant changes. | – |
| Langdahl and colleagues 24 | 2009 | Teriparatide versus alendronate for treating glucocorticoid‐induced osteoporosis: an analysis by gender and menopausal status | Men and women with GIO (with subgroup analysis on premenopausal women) | RCT | 20 μg TPTD versus alendronate 10 mg/day | 18 months | Premenopausal women receiving TPTD experienced greater increments in spinal BMD (7.0% versus 0.7%, p < 0.001) than those prescribed alendronate. | Vertebral fractures: 0 in premenopausal women. 12 teriparatide (9 postmenopausal, 2 premenopausal, 1 man) and 8 alendronate patients (6 postmenopausal, 2 men) |
| Roux and colleagues 144 | 2012 | Post hoc analysis of a single iv infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid‐induced osteoporosis | 18–85 year old adults exposed to ≥7.5 mg/day prednisolone for <3 (prevention subgroup) or ≥ 3 months (treatment subgroup) and expected to continue glucocorticoids for >1 year; subgroup analysis provided for premenopausal women and adults aged 35–50 years | RCT | 5 mg iv ZA single infusion and daily oral placebo versus 35 mg risedronate weekly and single placebo iv infusion | 12 months |
Greater improvement in hip BMD with ZA than risedronate in premenopausal women in both the tsreatment (p = 0.025) and prevention (p = 0.049) subpopulations. No significant differences in Risedronate versus ZA at the lumbar spine in premenopausal women. ZA significantly increased BMD at the spine at 12 months in premenopausal women, compared with risedronate, in both treatment (3.1% versus 1.7%) and prevention (1.8% versus 0.7%) subgroups. |
– |
| IOP | ||||||||
| Cohen and colleagues 145 | 2013 | Teriparatide for idiopathic osteoporosis in premenopausal women: a pilot study | 21 premenopausal women with IOP | Pre‐test post‐test interventional study (open‐label pilot study) | TPTD 20 μg daily for 18–24 months | 24 months | Increase in spinal (10.8 ± 8.3% [SD]), total hip (6.2 ± 5.6%), and femoral neck (7.6 ± 3.4%) (all p < 0.001) BMD increased at 24 months | – |
| Cohen and colleagues 146 | 2015 | Bone density after teriparatide discontinuation in premenopausal idiopathic osteoporosis | 15 premenopausal women with IOP who previously received 18–24 months of TPTD | Pre‐test post‐test | TPTD cessation | 2.0 ± 0.6 years | Decline in spinal BMD 4.8 ± 4.3% (p = 0.0007); stable BMD at femoral neck (−1.5 ± 4.2%) and total hip (−1.1 ± 3.7%) | – |
| Cohen and colleagues 175 | 2020 | Effect of teriparatide on bone remodeling and density in premenopausal idiopathic osteoporosis: a phase II trial | 41 premenopausal women with IOP | RCT | TPTD (6 months) versus placebo | 24 months |
6 month RCT: greater spinal BMD increase with TPTD (5.5%) versus placebo (1.5%; p < 0.01). 24 month follow up: TPTD increased spinal BMD (13.2%; 95% CI 10.3,16.2), total hip (5.2%; 95% CI 3.7, 6.7) and femoral neck (5%; 3.2, 6.7) at 24 months. |
– |
| PLO | ||||||||
| O'Sullivan and colleagues 147 | 2006 | Bisphosphonates in pregnancy and lactation‐associated osteoporosis | 10 women with fragility vertebral fractures presenting at a median of 1 month postpartum | Case series | Bisphosphonates (n = 9; 5 within 1 year of presentation) | 1–19 years | Increase in spinal BMD (23%) after 2 years of treatment in women receiving bisphosphonate within 1 year of presentation (n = 5) | Postpartum fracture in 5 women (4/5 received bisphosphonates); n = 2 sustained fracture outside of pregnancy over subsequent 10 years |
| Choe and colleagues 125 | 2012 | Effect of teriparatide on pregnancy and lactation‐associated osteoporosis with multiple vertebral fractures | 3 women with PLO and multiple vertebral fractures | Case series | TPTD for 18 months | 18 months (completion of treatment) | Increased spinal (19.5%; range: 14.5–25%) and femoral neck (13.1%; range: 9.5–16.7%) BMD after 18 months | No fractures during period of treatment |
| Laroche and colleagues 148 | 2017 | Pregnancy‐related fractures: a retrospective study of a French cohort of 52 patients and review of the literature | 52 women with fracture during pregnancy or in the 6 months post‐partum | Case control study | Bisphosphonates (n = 19) for 2–3 years or TPTD 20 μg (n = 11) for 18 months or strontium ranelate (n = 2) for 2 years | Mean follow‐up 2.5 years | Annual mean gain of 10.2% in spinal BMD and 2.6% at the femoral neck with bisphosphonates; annual mean gain of 14.9% in the spine with TPTD and 5.6% at the femoral neck. Annual mean gain of 6.6% at the spine and 2.3% at the femoral neck in controls | 10/52 (19.2%) fractured during following (4–36 months); 3 received bisphosphonates, 1 had received TPTD. Repeat fractures during pregnancy in 2/7 who conceived again. |
| Hong and colleagues 124 | 2018 | Changes in bone mineral density and bone turnover markers during treatment with teriparatide in pregnancy‐ and lactation‐associated osteoporosis | 32 women with PLO and vertebral fractures | Retrospective cohort study | TPTD 20 μg subcutaneous for 12 months (n = 27) versus no TPTD (n = 5) | 12 months (to completion of treatment) | Greater increase in spinal BMD in TPTD treated women versus untreated controls (15.5 ± 6.6% versus 7.5 ± 7.1%, p = 0.020) | – |
| Lee and colleagues 149 | 2021 | Bone density after teriparatide discontinuation with or without antiresorptive therapy in pregnancy‐ and lactation‐associated osteoporosis | 33 women with PLO | Retrospective cohort study | TPTD for a median of 12 months with (n = 13) or without (n = 20) sequential anti‐resorptive therapy ((alendronate [n = 3], denosumab [n = 4], ibandronate [n = 3], risedronate [n = 2], and zoledronic acid [n = 1]; median 18 months) | Median 18 months post course of TPTD | No difference in mean spinal BMD between patients treated with antiresorptive therapy versus those not treated with antiresorptives. | No fractures in subsequent pregnancies |
| Lampropoulou‐Adamidou and colleagues 150 | 2021 | Teriparatide treatment in patients with pregnancy‐and lactation‐associated osteoporosis | 19 premenopausal women with PLO | Retrospective cohort study | TPTD + calcium + vitamin D (n = 19) versus calcium + vitamin D (n = 8) for 24 months | 24 months (to completion of treatment) | aBMD increase of 20.9 ± 11.9% (TPTD) versus 6.2 ± 4.8% (control) at the LS (p < 0.001), 10.0 ± 11.6% versus 5.8 ± 2.8% at the TH (p = 0.43) | Median of 4.0 (3–9) VFs in TPTD group versus 2.5VFs (1–10) p = 0.02 |
| Solid‐organ tumors | ||||||||
| Gnant and colleagues 151 | 2007 | Zoledronic acid prevents cancer treatment‐induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone‐responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group | 401 premenopausal women with hormone‐responsive breast cancer | RCT | Tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± ZA (4 mg iv 6 monthly) versus anastrozole (1 mg/d orally) and goserelin ± ZA for 3 years | 3 years | ZA associated with stable BMD while patients not given ZA demonstrated bone loss after 3 years (−14.4%, p < 0.0001) | – |
| Gnant and colleagues 41 | 2008 | Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early‐stage breast cancer: 5‐year follow‐up of the ABCSG‐12 bone‐mineral density substudy | Premenopausal women with endocrine‐responsive breast cancer receiving adjuvant endocrine therapy (goserelin and anastrozole or goserelin and tamoxifen) | RCT | 4 mg intravenous ZA every 6 months, then 4 mg every 6 months over 3 years (n = 899) versus no treatment (n = 904) | 60 months (median; range 15.5–96.6) | Greater BMD loss with anastrazole than tamoxifen, in patients not receiving ZA. (spinal −13.6% versus −9.0%, p < 0.0001). 2 years post treatment with ZA, decreased BMD again noted in those not exposed to ZA (spinal BMD ‐6.3%) while patients who received ZA had stable BMD at 36 months (+0.4%, trochanter at spine, +0.8% at trochanter) and increased BMD at 60 months (+4.0% at spine and + 3.9% at trochanter) | – |
| Hershman and colleagues 152 | 2008 | Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early‐stage breast cancer | 101 premenopausal women with breast cancer undergoing adjuvant chemotherapy | RCT | ZA 4 mg iv 3 monthly versus placebo for a year | 1 year | In patients randomized to ZA, BMD was stable at the LS (−0.03% at 24 weeks, −0.6% at 52 weeks), FN (+0.2% at 24 weeks, +0.4% at 52 weeks), and TH (−0.19 at 24 weeks, −0.12% at 52 weeks). In contrast, BMD was reduced with at the spine (−2.98% at 24 weeks and −4.39%) and total hip (−2.08% at 52 weeks) with placebo, significantly (p < 0.05) different to ZA. | – |
| Hines and colleagues 153 | 2009 | Phase III randomized, placebo‐controlled, double‐blind trial of risedronate for the prevention of bone loss in premenopausal women undergoing chemotherapy for primary breast cancer. | 216 premenopausal women undergoing adjuvant chemotherapy for breast cancer | RCT | Calcium 600 mg, Vitamin D 400 IU + risedronate 35 mg weekly or placebo | 12 months | No difference in mean BMD change at the spine (4.3% risedronate, 5.4% placebo at 1 year; p = 0.18) or femoral neck. | – |
| Kim et al | 2010 | Zoledronic acid prevents bone loss in premenopausal women with early breast cancer undergoing adjuvant chemotherapy: a phase III trial of the Korean Cancer Study Group (KCSGBR06‐01) | 112 premenopausal women aged >40 years undergoing adjuvant chemotherapy for early stage hormone + breast cancer | RCT | 4 mg iv ZA 6 monthly (n = 56) versus observation (delayed ZA till fragility fracture or spinal/hip BMD T‐score ≤ −2.5 at 6 month review (n = 56)) | 12 months (treatment completion) | Stability in spinal (+0.5% ± 3.2% at 6 months, −1.1 ± 3.7% at 12 months) and femoral neck (+0.4 ± 4.4% at 6 months and + 1.1 ± 5.6% at 12 months) BMD with ZA and reduction in BMD at spinal (−3.1 ± 4.8%, p < 0.001 at 6 months and −7.5 ± 2.8%, p < 0.001 at 12 months) and femoral neck (−1.1 ± 3.4%, p = 0.044 at 6 months and −3.4 ± 3.3%, p < 0.001 at 12 months) BMD with observation | – |
| Kim and colleagues 154 | 2011 | Zoledronic acid prevents bone loss in premenopausal women with early breast cancer undergoing adjuvant chemotherapy: a phase III trial of the Korean Cancer Study Group (KCSG‐BR06‐01) | Premenopausal >40 years women with early breast cancer receiving adjuvant chemotherapy | RCT | Upfront ZA 4 mg iv 6 monthly (n = 57) versus delayed ZA (observation; n = 59) | 12 months | ZA prevented spinal BMD loss (−1.1% with ZA versus −7.5% with observation group at 12 months. Between group difference of difference in % change from baseline: Differences 6.4% for the LS, and 3.6% for the femoral neck. | – |
| Shapiro and colleagues 42 | 2011 | Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: final results from CALGB trial 79809 | 439 premenopausal women with chemotherapy induced ovarian failure | RCT | ZA 4 mg 3 monthly for 2 years commenced within 1–3 months or after 1 year of chemotherapy initiation | 3 years | Less bone loss at 12 months in women randomized to ZA at initiation of chemotherapy (median + 1.2% versus −6.7%, p < 0.001 in women with chemotherapy induced ovarian failure, and median + 1.4% versus −5.5, p < 0.001 in all women). Less bone loss at 3 years in women who received ZA at initiation of chemotherapy (median + 1% versus ‐0.5%, p = 0.019). | – |
| Hadji and colleagues 155 | 2014 | Effects of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for HR+ breast cancer: the ProBONE II study | 70 premenopausal women with early BC receiving adjuvant chemotherapy and/or endocrine therapy | RCT | 4 mg iv ZA (n = 34) versus placebo (n = 36) over 2 years | 24 months (treatment completion) | Increased spinal BMD 3.14% from baseline to 24 months with ZA versus a 6.43% decrease with placebo p < 0.0001). Increased BMD also at the femoral neck (right:1.22% and left: 0.74%) while reduction in BMD seen at these sites (−2.38% p < 0.0001 and −2.28%, p < 0.002). | 1 traumatic rib fracture (ZA) |
| Kalder and colleagues 156 | 2015 | Effects of zoledronic acid versus placebo on bone mineral density and bone texture analysis assessed by the trabecular bone score in premenopausal women with breast cancer treatment‐induced bone loss: results of the ProBONE II substudy | 70 premenopausal women with ER positive and/or PR positive BC considered for adjuvant/neoadjuvant chemotherapy and/or adjuvant endocrine therapy | RCT | 4 mg iv ZA 3 monthly (n = 34) versus placebo (n = 36) for 2 years | 24 months (treatment completion) | Significant increase in spinal BMD with ZOL at 12 and 24 months (2.17%, p < 0.001 and 3.14%, p < 0.001). Significant decrease in spinal BMD with placebo at 12 and 24 months (−5.02%, p < 0.001 and 6.43%, p < 0.001). | – |
| Kyvernitakis and colleagues 157 | 2018 | Prevention of breast cancer treatment‐induced bone loss in premenopausal women treated with zoledronic acid: final 5‐year results from the randomized, double‐blind, placebo‐controlled ProBONE II trial. | Premenopausal women with early BC receiving adjuvant chemotherapy and/or endocrine therapy | RCT | 4 mg iv ZA every 3 months (n = 34) versus placebo (n = 36) over 2 years | 60 months | ZA prevented treatment‐induced bone loss: Spinal BMD increase by 2.9% with ZA versus 7.1% decrease in placebo‐treated patients. Over 60 months, 2.2% decrease in spinal BMD in ZA patients versus 7.3% decline in placebo‐treated patients (p < 0.001) | – |
| Coleman and colleagues 158 | 2021 | Bone health outcomes from the international, multicenter, randomized, phase 3, placebo‐controlled D‐CARE study assessing adjuvant denosumab in early breast cancer | Women with stage II/III breast cancer receiving neo/adjuvant chemotherapy. Subgroup analysis based on menopausal status provided. | RCT | Denosumab (n = 2256) or placebo (n = 2253) 3–4 weekly for 6 months and then every 3 months for 5 years | 5 years from commencement | ‐ | HR for time to on‐study fracture 0.74 (0.56–0.99) in favor of denosumab |
| Other | ||||||||
| Palomba and colleagues 159 | 2002 | Raloxifene administration in women treated with gonadotropin‐releasing hormone agonist for uterine leiomyomas: effects of bone metabolism | 100 premenopausal women with uterine leiomyomas treated with leuprolide acetate | RCT | Raloxifene 60 mg/day versus placebo | 42 weeks | No change in BMD at 42 weeks in women treated with raloxifene; ~1%/month reduction in BMD noted in women not treated with raloxifene | – |
| Mitwally and colleagues 160 | 2002 | Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add‐back in long‐term GnRH‐agonist down‐regulated patients with endometriosis and premenstrual syndrome | 15 premenopausal women with endometriosis and 5 with severe premenstrual syndrome (PMS) receiving leuprolide depot 1.75 mg im | Pre‐test post‐test study | 1 mg oral micronized estradiol daily and 0.35 mg norethindrone daily for 2 days alternating with 2 days without norethindrone.(commenced at 2–3 months for endometriosis patients and 1 month for PMS patients) | 31.2 ± 17 months (for endometriosis patients) and 37.7 ± 8.4 (PMS patients) | No significant change in spinal or femoral neck BMD | – |
| Cundy and colleagues 161 | 2003 | A randomized controlled trial of estrogen replacement therapy in long‐term users of depot medroxyprogesterone acetate | 38 premenopausal women with min. 2 year DMPA use and spinal BMD T‐score ≤ 0 | RCT | 0.625 mg conjugated estrogen versus placebo | 24 months | Increase in spinal BMD in the estrogen‐treated group (1%) and reduction in BMD in the placebo group (−2.6%; 3.5% between‐group difference at 24 months). No significant difference at the femoral neck. | – |
| Aris and colleagues 162 | 2004 | Efficacy of alendronate in adults with cystic fibrosis with low bone density | Adults with CF | RCT | Alendronate 10 mg/day (n = 24) orally versus placebo (n = 24) for 1 year | 12 months | Increased spinal (4.9 ± 3.0%; p < 0.001) and hip (2.8 ± 3.2%, p = 0.003) BMD with alendronate. Loss of BMD at the spine (−1.8 ± 4.0%) and hip (−0.7 ± 4.7%). | – |
| Ripps and colleagues 163 | 2003 | Alendronate for the prevention of bone mineral loss during gonadotropin‐releasing hormone agonist therapy | 11 premenopausal women commenced on GnRHa therapy | RCT | Alendronate 10 mg/d versus placebo for 6 months | 6 months | Mean increase in spinal BMD of 1.0% (p = 0.35) with alendronate and a loss of 3.8% (p = 0.01) with placebo. Stable hip BMD with alendronate (−0.4%, p = 0.65) versus reduction in BMD (−3.4%, p = 0.02) with placebo.. | – |
| Adami and colleagues 164 | 2009 | Intravenous neridronate in adults with osteogenesis imperfecta | 23 men and 23 premenopausal women (18–50 years) with OI | RCT | 100 mg iv neridronate 3 monthly versus no treatment (calcium and vitamin D supplemented if deficient) | 24 months | Increase in spinal (3.0 ± 4.6% (SD)) and hip BMD (4.3 ± 3.9%), in neridronate treated patients within the first 12 months versus no significant change in untreated patients, | VF RR in neridronate treated patients 0.14 (p = 0.03) |
| Chapman and colleagues 165 | 2009 | Intravenous zoledronate improves bone density in adults with cystic fibrosis | 22 adults with CF (non‐transplanted) | RCT | 2 mg iv ZA (n = 10) or placebo (n = 12) 3 monthly for 2 years. All received calcium and vitamin D | 2 years from commencement | Spinal BMD increase greater with ZA (6.14% ± 1.86) than placebo (0.44 ± 0.10; p = 0.021) at 24 months. Similar findings at the femoral neck (4.23% ± 1.3 versus −2.5% ± 1.41, p = 0.0028) | Nil fractures in either group |
| Kacker and colleagues 166 | 2014 | Bone mineral density and response to treatment in men younger than 50 years with testosterone deficiency and sexual dysfunction or infertility | 75 men aged <50 years with total testosterone <12.1 nmol/L or free testosterone with sexual dysfunction or infertility | Cohort study | Testosterone cypionate (n = 43) at initial dose of 100 mg weekly or 200 mg biweekly OR testosterone pellets 750 – 900 mg 3 monthly versus clomiphene citrate (n = 17) 25 mg daily or 50 mg 3 times a week versus anastrazole (n = 3) | 30.4 ± 16.2 months | Increased spinal (+0.0306 ± 0.0392 g/cm2, p < 0.001) but not hip BMD in men treated with testosterone; reduced spinal BMD) in men treated with clomiphene citrate (−0.0144 ± 0.0199, p = 0.0089). No significant change (−0.058 ± 0.0331, p = 0.094 spinal BMD; 0.0145 ± 0.0462, p = 0.76 total hip BMD) in men treated with anastrazole | – |
| Yassin. and colleagues 167 | 2014 | Effects of the anti‐receptor activator of nuclear factor kappa B ligand denosumab on beta thalassemia major‐induced osteoporosis | 30 patients aged 18–32 years with beta‐thalassemia major induced osteoporosis | Pre‐test post‐test interventional study | 60 mg subcutaneous denosumab 6 monthly | 12 months | 9.2% (95% CI 8.2–10.1%) increase in spinal BMD at 12 months and 6.0% (95% CI 5.2–6.7%) increase at the femoral neck | – |
AN = anorexia nervosa; BC = breast cancer; bd = twice per day; BMD = bone mineral density; CF = cystic fibrosis; CI = confidence interval; DMPA = depot medroxyprogesterone; ER = estrogen receptor; GnRHa = gonadotropin releasing hormone agonist; IOP = idiopathic osteoporosis; iv = intravenous; OI = osteogenesis imperfecta; PLO = pregnancy and lactation associated osteoporosis; PMS = premenstrual syndrome; PR = progesterone receptor; RCT= randomized controlled trial; SD = standard deviation; SLE = systemic lupus erythematosus; TPTD = teriparatide; VF = vertebral fracture; YAM = young adult mean; ZA= zoledronic acid.